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1.
Artigo em Chinês | WPRIM | ID: wpr-960907

RESUMO

ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets (TWPT) by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis (RA) and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts, the "efficacy-toxicity" association network of TWPT was constructed, and the key network targets were identified by calculating the topological values of the nodes, including the degree, closeness and betweenness. After that, the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes (58 up-regulated and 61 down-regulated) between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics, and 49 differentially expressed proteins (36 up-regulated and 13 down-regulated) were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition, the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine, and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore, the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically, the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance, especially playing an important role in neutrophil degranulation, complement cascade reaction, and immune-inflammatory response mediated by protein post-translational modification. Notably, the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation, such as RAS and mitogen-activated protein kinase (MAPK) signaling pathway, and in several liver functional processes, such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics, transcriptomics and proteomics, laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.

2.
Pak J Pharm Sci ; 34(2): 649-656, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34275842

RESUMO

Studied the optimum extraction process of polysaccharide from Phaeoporus obliquus and the effect of Phaeoporus obliquus polysaccharide on carbon tetrachloride (CCl4)- or alcohol-induced acute liver injury in mice. The main factor in influencing the extraction rate of Phaeoporus obliquus polysaccharide were extraction power and time, which was a kind of pyran glucose by infrared spectroscopy. CCl4 and alcohol were employed respectively to establish CCl4 and alcohol-induced acute liver injury mouse models. Compared with model groups mice, Phaeoporus obliquus polysaccharide treatment at the doses of 100mg/kg and 200mg/kg exhibited an obvious reduction liver index, ALP, ALT, AST levels, MDA content and TNF-α level (p<0.01) and SOD activity was increased, which was in a dose-dependent manner. Compared with the model group, the necrosis degree of hepatocytes was obviously reduced and the small fat droplets were formed in some cytoplasm, especially in high dose group, which the liver cells recovered to the level of normal group. Rt-PCR results showed that the expression of CYP2E1 mRNA in liver tissues of Phaeoporus obliquus polysaccharide groups were significantly reduced, and the difference were statistically significant compared with the model group (p<0.05). These results demonstrated that Phaeoporus obliquus polysaccharide has significantly hepatoprotective effect on CCl4 and alcohol-induced acute liver injury in mice.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Polissacarídeos Fúngicos/farmacologia , Hepatócitos/efeitos dos fármacos , Inonotus , Hepatopatias Alcoólicas/metabolismo , Fígado/efeitos dos fármacos , Alanina Transaminase/efeitos dos fármacos , Alanina Transaminase/metabolismo , Fosfatase Alcalina/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Tetracloreto de Carbono/toxicidade , Depressores do Sistema Nervoso Central/toxicidade , Citocromo P-450 CYP2E1/efeitos dos fármacos , Citocromo P-450 CYP2E1/genética , Etanol/toxicidade , Hepatócitos/metabolismo , Hepatócitos/patologia , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Camundongos , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
3.
Artigo em Chinês | WPRIM | ID: wpr-888024

RESUMO

To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1β,IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1β,IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.


Assuntos
Humanos , Artrite Reumatoide/tratamento farmacológico , Linfócitos B , Cápsulas , Medicamentos de Ervas Chinesas , Fosfatidilinositol 3-Quinases , Fator A de Crescimento do Endotélio Vascular
4.
Artigo em Chinês | WPRIM | ID: wpr-828873

RESUMO

OBJECTIVE@#To explore the correlations of echocardiographic parameters in patients with gout.@*METHODS@#The hospitalization data and medical records of patients with gout between January, 2012 and June, 2019 were retrieved from the database of Anhui Provincial Hospital of Traditional Chinese Medicine, and the echocardiographic parameters and clinical laboratory test results of the inflammatory, immunological and metabolic indicators were analyzed. SPSS 22.0, SPSS Clementine 11.1 Aprior and other statistical software were used to determine the association rules and carry out correlation analysis, heat map analysis and multi-factor logistic regression analysis of the indicators.@*RESULTS@#Heat map analysis showed that the expressions of EF and SV were the most significant, followed by AODd, LADs, LVDd and FS. Cluster analysis showed that AODd, EF, FS, LADs, LVDd, and SV were all in cluster 1, and IVSTd, LVPWTd, MPAD, Pmax, and RVDd were in cluster 2. Correlation analysis showed that in the 383 patients, EF was negatively correlated with LVDd ( < 0.05) and positively correlated with FS and SV ( < 0.05); AODd was positively correlated with IVSTd, LADs, LVDd, LVPWTd, RVDd, SV, and ESR ( < 0.05); FS was positively correlated with EF and SV ( < 0.05) and negatively correlated with LVDd ( < 0.05);IVSTd was positively correlated with AODd, LADs, LVPWTd, and complement C4 ( < 0.05); LADs were positively correlated with AODd, IVSTd, MPAD, RVDd, and SV ( < 0.05); LVDd was positively correlated with AODd, IVSTd ( < 0.05), and negatively correlated with LVDd and complement C3 ( < 0.05); MPAD and LADs, HDLC and TC were positively correlated ( < 0.05)and negatively correlated with Pmax ( < 0.05); Pmax was positively correlated with LVDd, RVDd and SV ( < 0.05)and negatively correlated with FS and MPAD ( < 0.05); RVDd was positively correlated with AODd, LADs, LVDd, Pmax, SV ( < 0.05); SV was positively correlated with AODd, EF, LADs, LVDd, Pmax, and RVDd ( < 0.05); complement C3 was positively correlated with complement C4 and CRP ( < 0.05), and negatively correlated with LVPWTd ( < 0.05); complement C4 was positively correlated with IVSTd, complement C3, CRP, and ESR ( < 0.05); CRP was positively correlated with complement C3, complement C4, IgA, IgG ( < 0.05), and negatively correlated with TC, HDLC, and TG ( < 0.05); TG was positively correlated with HDLC, IgM, and TC ( < 0.05), and negatively correlated with CRP ( < 0.05); HDLC was positively correlated with MPAD, HDLC and TC ( < 0.05) and negatively correlated with CRP ( < 0.05); IgA was positively correlated with CRP, IgG and IgM ( < 0.05); IgG was positively correlated with CRP, IgA and IgM ( < 0.05); IgM is positively correlated with TG, IgA, IgG, UA ( < 0.05) and negatively correlated with CRP ( < 0.05); UA was positively correlated with IgM ( < 0.05); ESR was positively correlated with AODd and complement C4 ( < 0.05); HCY was negatively correlated with RVDd ( < 0.05); TC was positively correlated with MPAD and TG ( < 0.05), and negatively correlated with CRP ( < 0.05). The increase of Pmax was significantly associated with the increase of LDL-C, UA, complement C4, TG, HCY, HDL-C, IgG, ESR, CRP, and complement C3; the increase of SV was associated with the elevations of UA, LDL-C, complement C4, HDL-C, CRP, IgG, HCY, TC, ESR, TG, and complement C3. Multivariate logistic regression analysis indicated that FS was positively correlated with LDL-C ( < 0.05), Pmax was negatively correlated with IgM ( < 0.05), and SV was negatively correlated with ESR ( < 0.05).@*CONCLUSIONS@#The changes of echocardiographic parameters in patients with gout are correlated with the increase in inflammation, immunity, and metabolic indexes. Patients with a history of smoking and drinking do not show obvious changes in cardiac function. The changes in metabolic indexes are risk factors for changes in echocardiographic parameters.


Assuntos
Humanos , Ecocardiografia , Gota , Inflamação , Estudos Retrospectivos , Fatores de Risco
5.
Artigo em Inglês | WPRIM | ID: wpr-719641

RESUMO

Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was 24.0 µM and 17.8 µM for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentration-dependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.


Assuntos
Humanos , Acetilcisteína , Antineoplásicos , Proteínas Reguladoras de Apoptose , Apoptose , Artrite Reumatoide , Linhagem Celular , Elaeagnaceae , Fibroblastos , Pulmão , Potencial da Membrana Mitocondrial , Neoplasias Bucais , Plantas Medicinais , Espécies Reativas de Oxigênio
6.
Artigo em Chinês | WPRIM | ID: wpr-777518

RESUMO

To evaluate the effect of traditional Chinese medicine(TCM) invigorating spleen unit therapy on inflammatory markers of osteoarthritis(OA) patients by random walk model. The patient information was collected by the data processing system of medical records of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. In-patient information of the department of rheumatology of the hospital between June 2012 and December 2016 was collected and summarized. Based on the use of traditional Chinese medicine decoction and hospital-prepared compound Qiyi Capsules(Xinfeng Capsules),the patients were divided into the unit therapy group and the simple endotherapy group. The random walk model was used to evaluate the effect of traditional Chinese medicine invigorating spleen unit therapy on TCM spleen therapy unit(ESR) and high sensitive C reactive protein(hs-CRP). A total of 3 517 cases of OA patients met the study requirements. The simple endotherapy group had 1 771 cases(50. 36%),while the unit therapy group had 1 746 cases(49. 64%). The baseline data analysis showed that the general information of the cases,the TCM oral intake frequency and the core prescription information had no statistically significant difference,with comparability. The unit therapy group showed the maximum ESR stochastic volatility at 924,walking step number of 1 771,forward walking growth rate at 0. 264 5,ratio at3. 78,random fluctuation power law at 0. 306 5± 0. 076 8,positive increase rate of comprehensive evaluation index at 0. 264 5,and comprehensive evaluation index record number of 1 771; whereas the simple endotherapy group showed the maximum ESR random fluctuation value at 478,walking step number of 1 399,forward walking growth rate at 0. 152 4,ratio at 6. 56,random fluctuation power law at 0. 347 4±0. 101 7,positive increase rate of comprehensive evaluation index at 0. 152 4,and comprehensive evaluation index record number of 1 399. The unit therapy group showed the maximum hs-CRP random fluctuation value at 391,walking step number of1 081,forward walking growth rate at 0. 178 1,ratio at 5. 62,random fluctuation power law at 0. 343 6±0. 094 7,positive increase rate of comprehensive evaluation index at 0. 178 1,and comprehensive evaluation index record number of 1 081; while the simple endotherapy groups showed the maximum hs-CRP random fluctuation value at 210,walking step number of 797,forward walking growth rate at0. 113 2,ratio at 8. 83,random fluctuation power law at 0. 382 6±0. 109,positive increase rate of comprehensive evaluation index at0. 113 2,and comprehensive evaluation index record number of 797. According to our department of rheumatism,there was a longrange correlation between the two groups in the comprehensive evaluation index and the intervention measures. TCM spleen strengthening unit therapy has a better effect in alleviating the inflammatory index of OA than traditional Chinese medicine.


Assuntos
Humanos , Biomarcadores , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Inflamação , Diagnóstico , Medicina Tradicional Chinesa , Osteoartrite , Tratamento Farmacológico , Baço
7.
Artigo em Chinês | WPRIM | ID: wpr-773824

RESUMO

OBJECTIVE@#To study the effect of soothing liver, relieving depression, invigorating spleen and reinforcing blood on reducing delirium in elderly patients with hip fracture.@*METHODS@#From December 2014 to June 2018, 180 elderly patients with hip fracture admitted were divided into treatment group and placebo group according to the order of admission:90 patients in treatment group were treated with Jiawei Xiaoyao Powder(JWXYP), including 32 males and 58 females, with an average age of(72.12±4.92), involving 67 cases of femoral trochanter fractures and 23 cases of femoral neck fractures; 35 cases underwent dynamic hip screw fixation, 31 cases underwent intramedullary fixation and 24 cases underwent artificial hip replacement. In the placebo group, 90 patients were treated with placebo, including 37 males and 53 females, with an average age of(72.91±5.43) years old, involving 69 cases of femoral trochanteric fractures and 21 cases of femoral neck fractures, including 37 cases underwent dynamic hip screw fixation, 30 cases underwent intramedullary fixation and 23 cases underwent artificial hip replacement. The age, sex, injury site, intraoperative bleeding volume, postoperative drainage, operation time, anesthesia time, post-operative pain score, post-operative hemoglobin, post-operative CRP, delirium severity(DRS) score and delirium occurrence were observed and compared between the two groups.@*RESULTS@#All patients were followed up until delirium returned to normal, postoperative delirium was found in 12 cases (13.33%) in the treatment group and in 39 cases(43.33%) in the placebo group, the treatment group was significantly better than the placebo group. The monitoring indexes of the two groups were compared:post-operative pain score(=0.002), post-operative hemoglobin(=0.012), post-operative CRP(=0.042).@*CONCLUSIONS@#JWXYP can relieve liver depression, invigorate spleen and invigorate blood circulation, reduce pain, inflammatory stimulation and supplement blood volume after operation, and significantly reduce the incidence of delirium after operation.


Assuntos
Idoso , Feminino , Humanos , Masculino , Delírio , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Fixação Interna de Fraturas , Fraturas do Quadril , Cirurgia Geral , Resultado do Tratamento
8.
Drug Deliv ; 25(1): 1-11, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29214887

RESUMO

Hepatic macrophages have been considered as a therapeutic target for liver fibrosis treatment, and phosphatidylserine (PS)-containing nanoparticles are commonly used to mimic apoptotic cells that can specifically regulate macrophage functions, resulting in anti-inflammatory effects. This study was designed to test the efficacy of PS-modified nanostructured lipid carriers (mNLCs) containing curcumin (Cur) (Cur-mNLCs) in the treatment of liver fibrosis in a rat model. Carbon tetrachloride-induced liver fibrosis in rats was used as an experimental model, and the severity of the disease was examined by both biochemical and histological methods. Here, we showed that mNLCs were spherical nanoparticles with decreased negative zeta potentials due to PS decoration, and significantly increased both mean residence time and area under the curve of Cur. In the rats with liver fibrosis, PS-modification of NLCs enhanced the nanoparticles targeting to the diseased liver, which was evidenced by their highest accumulation in the liver. As compared to all the controls, Cur-mNLCs were significantly more effective at reducing the liver damage and fibrosis, which were indicated by in Cur-mNLCs-treated rats the least increase in liver enzymes and pro-inflammatory cytokines in the circulation, along with the least increase in collagen fibers and alpha smooth muscle actin and the most increased hepatocyte growth factors (HGF) and matrix metalloprotease (MMP) two in the livers. In conclusion, PS-modified NLCs nanoparticles prolonged the retention time of Cur, and enhanced its bioavailability and delivery efficiency to the livers, resulting in reduced liver fibrosis and up-regulating hepatic expression of HGF and MMP-2.


Assuntos
Curcumina/química , Curcumina/farmacologia , Cirrose Hepática/tratamento farmacológico , Nanopartículas/química , Fosfatidilserinas/química , Animais , Tetracloreto de Carbono/farmacologia , Fator de Crescimento de Hepatócito/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metaloproteinases da Matriz/metabolismo , Nanoestruturas/química , Ratos , Ratos Sprague-Dawley
9.
Artigo em Chinês | WPRIM | ID: wpr-696124

RESUMO

This study was aimed to explore traditional Chinese medicine (TCM) compatibility patterns or rules in the treatment of ankylosing spondylitis (AS) in the real world clinical situations.The effect of TCM treatment and immune inflammatory biomarkers were analyzed by association rules,which provided evidences for AS syndrome differentiation and treatment.Retrospective study was conducted on records of hospitalized AS patients at the Department of Rheumatism,the First Affiliated Hospital of Anhui University of Chinese Medicine from June 2012 to June 2016.The technology for complex networks was integrated to analyze the core prescription.The frequency and association rules of prescription patterns were analyzed using the SPSS 21.0 and SPSS modeler 14.2.The effect on immune inflammatory biomarkers was analyzed by association rules and random walk model.The results showed that,(1) warm,cold,and neutral herbs,sweet,bitter or pungent herbs,and with the channel tropism of spleen channel,stomach channel and liver channel are the most frequently prescribed herbs;(2) herbs with functions of tonifying and replenishing,blood-activating and stasis-resolving,qi-regulating,spleen-strengthening and dampness-resolving,wind-dampness dispelling,heatclearing are frequently prescribed,which are also interrelated and interacted on each other;(3) the top five pairs of couplet herbs with the highest confidence included Hong Hua paired with Tao Ren (98.15%),Yi Yi Ren paired with Fu Ling (95.47%),Gan Cao paired Gou Ji (94.57%),Gan Cao paired with Wei Ling Xian (94.48%),Pu Gong Ying paired Bai Hua She She Cao (94.40%);(4) Shan Yao was highly related to decreased C3,C4 and hs-CRP when compatibility with Fu Ling,Niu Xi,Ze Xie;Gou Ji was highly related to decreased IgA,IgG and IgM when compatibility with Bai Hua She She Cao,Chuan Xiong,Shah Yao.Xi Qian Cao was associated with Niu Xi when ESR and WBC decreased.Gou Ji and Du Huo were associated when SOD increased.(5) The group of internal medicine coordinated with external medicine has positive growth rate of walk and improvement index of inflammatory indexes (ESR,hs-CRP) compared to single internal medicine group.It was concluded that AS treatment in the Department of Rheumatism of our hospital was based on spleen.The treatment was focused on the regulation of cold and warm,sweet and bitter,liver and spleen.The treatment of AS is to eliminate evil factors and to reinforce healthy qi.TCM has advantages in the improvement of immune inflammatory indexes.The improvement of inflammatory indexes by the internal medicine coordinated with external medicine was better than the single use of internal medicine,which is worthy of further promotion.

10.
Artigo em Inglês | WPRIM | ID: wpr-229535

RESUMO

<p><b>OBJECTIVE</b>To determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function.</p><p><b>METHODS</b>This was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated.</p><p><b>RESULTS</b>Pain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>XFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients.</p>


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artrite Reumatoide , Sangue , Tratamento Farmacológico , Patologia , Sedimentação Sanguínea , Proteína C-Reativa , Cápsulas , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Articulações , Patologia , Qualidade de Vida , Testes de Função Respiratória , Inquéritos e Questionários , Resultado do Tratamento
11.
Artigo em Chinês | WPRIM | ID: wpr-951348

RESUMO

Objective To study the effects of Traditional Chinese Medicine Jianpi Chushi decoction and ointment on chronic eczema. Methods DNCB acetone solution was used to sensitize the skin of back and ears of 36 rats in order to establish chronic eczema model. A total of 36 rats were divided into four groups of 9 randomly including oral medicine group, external inunctum group, combination therapy group, and model control group respectively. Besides, the blank group of 4 healthy rats were set. The oral medicine group was given Traditional Chinese Medicine Jianpi Chushi decoction [(Poria cocos, Chinese yam, Cortex dictamni, Zaocys dhumnade, Rhizoma atractylodis, Pericarpium citri reticulatae, Scutellaria baicalensis, Radix Sophorae Flavescentis, Raw Radix Paeoniae Alba, Licorice roots (Northwest Origin)] by gastric infusion (1.6 g/mL·5 mL/d); the external inunctum group was given Qingpeng ointment on the skin, the combination therapy group was given Jianpi Chushi decoction by gastric infusion and Qingpeng ointment combination therapy. The model control group was given normal saline (NS) of the same volume by gastric infusion and vaseline on skin. Continuous administration 15 d and stopped for 3 d. The thickness difference and weight difference of left and right ear of every group were measured and the degree of ear swelling were evaluated. The CD4+ and CD8+ content and the IL-2, IL-4 level of serum were detected, and the inflammatory cells counts of back skin were recorded. Results After treatment, the degree of ear swelling of oral medicine group, external inunctum group and combination therapy group significant decreased compared with model control group (P < 0.05). The CD4+, CD8+ cell content and IL-2 level of oral medicine group, external inunctum group, combination therapy group and model control group significant decreased compared with blank group, and IL-2 level and the inflammatory cells count increased. After 15 d of treatment, the CD4+, CD8+ cell content and IL-2 level of serum of oral medicine group, external inunctum group and combination therapy group raised and the IL-4 level and the inflammatory cells count had significant decreased compared with model control group, and the effect of combination therapy group was more obvious (P < 0.05). Conclusions Qral Jianpi Chushi decoction could treat chronic eczema effectively, and oral Chinese medicine combined with ointment could enhance and speed up the efficacy.

12.
Artigo em Inglês | WPRIM | ID: wpr-819890

RESUMO

OBJECTIVE@#To study the effects of Traditional Chinese Medicine Jianpi Chushi decoction and ointment on chronic eczema.@*METHODS@#DNCB acetone solution was used to sensitize the skin of back and ears of 36 rats in order to establish chronic eczema model. A total of 36 rats were divided into four groups of 9 randomly including oral medicine group, external inunctum group, combination therapy group, and model control group respectively. Besides, the blank group of 4 healthy rats were set. The oral medicine group was given Traditional Chinese Medicine Jianpi Chushi decoction [(Poria cocos, Chinese yam, Cortex dictamni, Zaocys dhumnade, Rhizoma atractylodis, Pericarpium citri reticulatae, Scutellaria baicalensis, Radix Sophorae Flavescentis, Raw Radix Paeoniae Alba, Licorice roots (Northwest Origin)] by gastric infusion (1.6 g/mL·5 mL/d); the external inunctum group was given Qingpeng ointment on the skin, the combination therapy group was given Jianpi Chushi decoction by gastric infusion and Qingpeng ointment combination therapy. The model control group was given normal saline (NS) of the same volume by gastric infusion and vaseline on skin. Continuous administration 15 d and stopped for 3 d. The thickness difference and weight difference of left and right ear of every group were measured and the degree of ear swelling were evaluated. The CD4+ and CD8+ content and the IL-2, IL-4 level of serum were detected, and the inflammatory cells counts of back skin were recorded.@*RESULTS@#After treatment, the degree of ear swelling of oral medicine group, external inunctum group and combination therapy group significant decreased compared with model control group (P < 0.05). The CD4+, CD8+ cell content and IL-2 level of oral medicine group, external inunctum group, combination therapy group and model control group significant decreased compared with blank group, and IL-2 level and the inflammatory cells count increased. After 15 d of treatment, the CD4+, CD8+ cell content and IL-2 level of serum of oral medicine group, external inunctum group and combination therapy group raised and the IL-4 level and the inflammatory cells count had significant decreased compared with model control group, and the effect of combination therapy group was more obvious (P < 0.05).@*CONCLUSIONS@#Qral Jianpi Chushi decoction could treat chronic eczema effectively, and oral Chinese medicine combined with ointment could enhance and speed up the efficacy.

13.
Artigo em Chinês | WPRIM | ID: wpr-328311

RESUMO

<p><b>OBJECTIVE</b>To observe the effect of Xinfeng Capsule (XFC) on ankylosing spondylitis (AS) patients' symptoms and signs, serum immunoglobulin levels, peripheral blood lymphocyte autophagy protein, autophagy gene, and to explore its mechanism.</p><p><b>METHODS</b>Totally 59 AS patients were assigned to the treatment group (39 cases) and the control group (20 cases) according to random digit table. Patients in the treatment group received XFC, 0.5 g each pill, three pills each time, 3 times per day, while those in the control group received sulfasalazine (SASP), 0.25 g per tablet, 4 tablets each time, twice per day. Three months consisted of one therapeutic course. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were statistically calculated. Serum immunoglobulins (IgG1, IgG2, IgG3, IgG4, IgA , SIgA, and IgM) were detected using ELISA. Changes of Beclin1, LC3-II, phosphatidylinositol 3-kinase (PI3K), Akt, the mammalian target of rapamycin (mTOR) were detected using Western blot. Serum autophagy related genes such as Atg1, Atg5, Atg12, Atg13, and Atg17 were detected using the polymerase chain reaction (PCR). The correlation between immunoglobulin subtypes and autophagy gene in AS patients using Spearman correlation.</p><p><b>RESULTS</b>Compared with before treatment, BASDAI, IgG1, lgG3, and IgA decreased (P < 0.01); PI3K, Akt, and mTOR protein expressions decreased (P < 0.01); ATG1, ATG12, ATG13, and ATG17 mRNA expressions decreased, ATG5 mRNA expression increased (P < 0.01) in the treatment group. But BASDAI, IgG1, and IgA levels decreased (P < 0.05, P < 0.01); PI3K, Akt, and mTOR protein expressions decreased (P < 0.05); ATG1 and ATG13 mRNA expressions decreased (P < 0.05, P < 0.01) in the control group. Compared with the control group, BASDAI, IgG1, and IgA levels decreased (P < 0.05); PI3K, Akt, mTOR protein expressions decreased (P < 0.01); ATG12 and ATG17 mRNA expression decreased, ATG5 mRNA expression increased (P < 0.01) in the XFC group. Correlation analysis showed AS patients' IgG1, IgG2, IgG3, IgA, SIgA, IgM had negative correlation with ATG17; IgG4 and ATG17 were positively correlated (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>XFC could elevate clinical efficacy of AS patients and enhance their autophagy, which might be achieved by acting on PI3K/Akt/mTOR signal, affecting autophagy gene and autophagy protein expression, taking part in the regulation of proliferation and differentiation of lymphocyte B, and strengthen humoral immunity.</p>


Assuntos
Humanos , Proteínas Reguladoras de Apoptose , Metabolismo , Autofagia , Proteína Beclina-1 , Cápsulas , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Imunoglobulina A , Sangue , Imunoglobulina G , Sangue , Imunoglobulina M , Sangue , Linfócitos , Proteínas de Membrana , Metabolismo , Fosfatidilinositol 3-Quinases , Metabolismo , Espondilite Anquilosante , Tratamento Farmacológico , Sulfassalazina , Usos Terapêuticos , Serina-Treonina Quinases TOR , Metabolismo
14.
Molecules ; 20(11): 20569-81, 2015 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-26610438

RESUMO

Ardipusilloside-I (ADS-I) is a triterpenoid saponin extracted from Ardisia pusilla DC, and has been demonstrated to have potent antitumor activity. However, ADS-I metabolism in humans has not been investigated. In this study, we studied the biotransformation of ADS-I in human intestinal bacteria, and examined the in vitro antitumor activity of the major metabolites. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to detect ADS-I biotransformation products, and their chemical structures were identified by high performance liquid chromatography-nuclear magnetic resonance (HPLC-NMR). The antitumor activity of the major metabolites was determined by the MTT assay. Here, we show that main reaction seen in the metabolism of ADS-I in human intestinal bacteria was deglycosylation, which produced a total of four metabolites. The structures of the two major metabolites M1 and M2 were confirmed by using NMR. MTT assay showed that ADS-I metabolites M1 and M2 have the same levels of inhibitory activities as ADS-I in cultured SMMC-7721 cells and MCF-7 cells. In conclusion, this study demonstrates deglycosylation as a primary pathway of ADS-I metabolism in human intestinal bacteria, and suggests that the pharmacological activity of ADS-I may be mediated, at least in part, by its metabolites.


Assuntos
Antineoplásicos/farmacologia , Bactérias/metabolismo , Microbioma Gastrointestinal , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Saponinas/química , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
15.
Artigo em Chinês | WPRIM | ID: wpr-239222

RESUMO

<p><b>OBJECTIVE</b>To investigate the effects of electro-acupuncture (EA) on the expression of triggering receptor expressed on myeloid cell (TREM)l in ankle joint synovial tissue of acute gouty arthritis (AGA) rats.</p><p><b>METHODS</b>Forty male SD rats were randomly divided into 4 groups: normal, AGA, medication and EA group, 10 rats in each group. AGA model was established by induced monosodium urate (MSU) method, except the normal group. Tow days before AGA model was established, normal and AGA groups were lavaged with normal saline (20 ml/kg), medication group was lavaged with colchicine solution (20 ml/kg), EA(1.5-2 Hz, D.-D.wave, 9v; 1-3 rnA) was applied to "Sanyinjiao" (SP6), "jiexi" (ST41) and "Kunlun" (BL60) for 20 min, once daily;continuously for 9 days. Then observed the changes in dysfunction, and the content of TNF-α and IL-lβ detected by ELISA, the expression of TREM-l detected by immunohistochemistry and western blot.</p><p><b>RESULTS</b>Compared to the normal group, the AGA group of the dysfunction index increased significantly (P<0.01), the content of TNF-α and IL-lβ increased significantly (P<0.05), the expression of TREM-l in synovial tissue increased significantly (P<0.05); the medication and EA groups compared to the AGA group, the dysfunction index decreased significantly (P<0.01), the content of TNF-α and IL-lβ decreased significantly (P<0.05), the expression of TREM-l in synovial tissue decreased significantly (P<0.05); there were not statistically significant between the medication and EA group (P>0.05).</p><p><b>CONCLUSION</b>EA treating AGA may be through down-regulating the expression of TREM -1 in synovial tissue.</p>


Assuntos
Animais , Masculino , Ratos , Articulação do Tornozelo , Metabolismo , Patologia , Artrite Gotosa , Metabolismo , Terapêutica , Eletroacupuntura , Interleucina-1beta , Metabolismo , Ratos Sprague-Dawley , Receptores Imunológicos , Metabolismo , Membrana Sinovial , Metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides , Fator de Necrose Tumoral alfa , Metabolismo
16.
Artigo em Chinês | WPRIM | ID: wpr-237900

RESUMO

<p><b>OBJECTIVE</b>To explore the effect of Xinfeng Capsule (XC) on lipoprotein metabolism of rheumatoid arthritis (RA) patients.</p><p><b>METHODS</b>Totally 180 RA patients were assigned to the experimental group and the control group by random digit table, 90 in each group. Patients in the experimental group took XC (three pills each time, three times daily), while those in the control group took Methotrexate Tablet (four tablets each time, once per week). One month consisted of one therapeutic course and all patients were treated for two therapeutic courses. A healthy control group consisting of 60 patients was also set up. Changes of lipoprotein indices, clinical efficacy, lipid metabolism, joint symptoms and signs, activity indicators were observed, and correlation analyses were performed.</p><p><b>RESULTS</b>Compared with the healthy control group, expression levels of prealbumin (PA), globulin (GLO), high-density lipoprotein (HDL), apolipoprotein Al (Apo-A1) were lowered in RA patients (P <0. 05, P <0. 01). Correlation analyses showed that PA was negatively correlated with joint tenderness, morning stiffness time, disease activity score (DAS-28), C-reactive protein (CRP), interleukin (IL)-6, respectively. Total protein (TP) was negatively correlated with joint tenderness. GLO was negatively correlated with joint tenderness and DAS-28. HDL was negatively correlated with erythrocyte sedimentation rate (ESR) and endothelin (ET)-1. Apo-Al was negatively correlated with joint pain; Apo-B was negatively correlated with CRP; LDL was negatively correlated with morning stiffness time (P <0. 05, P <0. 01). Compared with before treatment, expression levels of PA, HDL, Apo-A1 , Apo-B, and serum IL-10 contents increased, and expression levels of ESR, CRP, IL-6, ET-1 , joint pain, joint swelling, morning stiffness time, and DAS-28 decreased in the experimental group (P <0. 05, P <0. 01). PA increased more after treatment than before treatment in the control group (P <0. 01). There was statistical difference in joint symptoms (except joint tenderness) and activity indices (except ET-1) in the control group (P <0. 05, P <0. 01). Compared with the control group after treatment, PA and HDL increased, ET-1 and duration of morning stiffness decreased in the experimental group (all P <0. 05).</p><p><b>CONCLUSIONS</b>Lipoprotein metabolic disorder exists in RA patients, and it is associated with disease activity. XC could obviously improve lipoprotein metabolism and joint symptoms.</p>


Assuntos
Humanos , Artrite Reumatoide , Tratamento Farmacológico , Metabolismo , Sedimentação Sanguínea , Proteína C-Reativa , Cápsulas , Medicamentos de Ervas Chinesas , Farmacologia , Usos Terapêuticos , Interleucina-10 , Interleucina-6 , Lipoproteínas , Lipoproteínas HDL , Metabolismo , Metotrexato
17.
Artigo em Chinês | WPRIM | ID: wpr-312984

RESUMO

<p><b>OBJECTIVE</b>To explore changes of B and T lymphocyte attenuator (BTLA), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAOC), reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA) in ankylosing spondylitis (AS) patients, and the effect of Xinfeng Capsule (XFC) on them.</p><p><b>METHODS</b>Totally 120 AS patients were assigned to two groups according to random digit table method, the XFC group (3 XFC pills each time, 3 times a day) and the SASP group (4 SASP tablets each time, twice a day), 60 in each group. All patients were treated for 3 months. Another 60 healthy subjects were recruited as a healthy control group. The expression frequency and activation levels of BTLA were detected using flow cytometry. Serum oxidative stress indices (such as SOD and CAT, TAOC, ROS, RNS, MDA) and contents of cytokines [tumor necrosis factor α (TNF-α), IL-1β, IL-4, and IL-10] were detected using enzyme-linked immunoassay (ELISA). Erythrocyte sedimentation rate (ESR) was detected using Westergren method. High-sensitivity C-reactive protein (Hs-CRP) was detected using HITACHI 7060 type automatic biochemical analyzer. Clinical efficacies of ASAS 20 and BASDAI50 were assessed using VAS. Correlation analysis between scoring for quality of life and BTLA expression frequency was performed.</p><p><b>RESULTS</b>(1) Clinical efficacies of ASAS 20 and BASDAI50 were significantly better in the XFC group than in the SASP group (P < 0.01). (2) Compared with the healthy control group, BTLA expressions in the peripheral blood of AS patients decreased significantly (P <0. 05); SOD, CAT, and TAOC values significantly decreased (P < 0.01, P < 0.05); ROS, RNS, and MDA values significantly increased (P < 0.01, P < 0.05); TNF-α, IL-1β, ESR, and Hs-CRP values significantly increased (P < 0.01); IL-4 and IL-10 values decreased significantly (P < 0.01, P < 0.05). (3) Compared with pre-treatment in the same group, BTLA/CD19 + B, BTLA/CD24 + B, SOD, TAOC, IL-4, SF-36 [physical functioning (PF), social functioning (SF), role limitation due to physical problems (RP), role limitation due to emotional problems (RE), body pain (BP), mental health (MH), vitality (VT), general health (GH)] were significantly elevated; ROS, MDA, TNF-α, ESR, Hs- CRP, VAS, BASDAI and BASFI, BAS-G were significantly lower in the peripheral blood of the two groups after treatment (P < 0.01, P < 0.05). Better effect was shown in the XFC group in elevating BTLA/CD19+ B, BTLA/CD24 + B, SOD, TAOC, IL-10, BP, MH, VT, and SF; and lowering ROS, IL-1β, MDA, TNF-α, ESR, Hs-CRP, VAS, BASDAI, BASFI, and BAS-G (P < 0.01, P < 0.05). (4) Pearson correlation analysis showed, BTLA/CD19 + B expression of the peripheral blood was positively correlated with SOD, CAT, TAOC, IL-4, IL-10, GH, RP, BP, and SF (r = 0.431, 0.325, 0.318, 0.316, 0.348, 0.314, 0.358, 0.318, 0.326, respectively, P < 0.05, P < 0.01), while it was negative correlated with ROS, MDA, TNF-α, IL-1β, ESR, VAS, and BASDAI (r = -0.342, -0.368, -0.334, -0.354, -0.324, -0.372, -0.342, respectively, P < 0.05, P < 0.01). BTLA/CD24 B expression of the peripheral blood was positively correlated with SOD, TAOC, IL-4, IL-10, GH, RP, BP, SF, RE, MH, VT (r = 0.358, 0.352, 0.372, 0.436, 0.435, 0.326, 0.352, 0.345, 0.326, 0.343, 0.332, respectively, P < 0.05, P < 0.01), while it was negative correlated with ROS, RNS, MDA, ESR, Hs-CRP, VAS, BASDAI, and BASFI (r = -0.447, -0.336, -0.405, -0. 395, -0. 358, -0.436, -0.338, -0.425, respectively, P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>XFC could improve BTLA expression in the peripheral blood of AS patients, negatively regulate activation and proliferation of B cells, and reduce abnormal immune responses and oxidative stress injury, thereby effectively alleviating joint stiffness and pain.</p>


Assuntos
Humanos , Linfócitos B , Fisiologia , Sedimentação Sanguínea , Proteína C-Reativa , Metabolismo , Cápsulas , Catalase , Metabolismo , Citocinas , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Citometria de Fluxo , Interleucina-10 , Metabolismo , Interleucina-1beta , Metabolismo , Interleucina-4 , Metabolismo , Malondialdeído , Metabolismo , Estresse Oxidativo , Qualidade de Vida , Espécies Reativas de Oxigênio , Espondilite Anquilosante , Tratamento Farmacológico , Superóxido Dismutase , Metabolismo , Linfócitos T , Fisiologia , Fator de Necrose Tumoral alfa , Metabolismo
18.
Artigo em Chinês | WPRIM | ID: wpr-333617

RESUMO

<p><b>OBJECTIVE</b>To investigate the effects of triptolide on Notch receptor and ligand expressions in rats with adjuvant-induced arthritis (AA).</p><p><b>METHODS</b>Forty rats were randomly divided into normal control (NC) group, model (MC) group, methotrexate group and triptolide groups. Rat models of AA were established by an intradermal injection of 0.1 mL Freund's complete adjuvant into the right paw. Twelve days after the injection, the rats were treated with corresponding drugs for 30 days; the rats in NC group and MC group were given saline only. Paw edema volume (E), arthritis index (AI), pulmonary function, histomorphologies, and Notch receptor/ ligand expression in the lung tissue were analyzed after the treatments.</p><p><b>RESULTS</b>Compared with the NC group, E, AI, Notch3, Notch4, and Delta1 expressions in the lung tissues significantly increased while pulmonary function and pulmonary expressions of Notch1, Jagged1, and Jagged2 significantly decreased the model rats (P<0.01). Compared with the MC group, triptolide-treated rats showed significantly improved pulmonary functions, increased expressions of Notch1, Jagged1, and Jagged2 and decreased expressions of Notch3, Notch4, and Delta1 in the lungs (P<0.05, P<0.01); the therapeutic effect of triptolide was better than that of methotrexate.</p><p><b>CONCLUSION</b>Triptolide can reduce inflammatory reaction and immune complex deposition to improve joint and pulmonary symptoms in rats with AA possibly by up-regulating the expressions of Notch3, Notch4, and Delta1 and down-regulating the expressions of Jagged1, Jagged2, and Notch1.</p>


Assuntos
Animais , Ratos , Artrite Experimental , Tratamento Farmacológico , Metabolismo , Proteínas de Ligação ao Cálcio , Metabolismo , Diterpenos , Farmacologia , Regulação para Baixo , Medicamentos de Ervas Chinesas , Compostos de Epóxi , Farmacologia , Peptídeos e Proteínas de Sinalização Intercelular , Metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Metabolismo , Proteína Jagged-1 , Proteína Jagged-2 , Ligantes , Pulmão , Metabolismo , Proteínas de Membrana , Metabolismo , Metotrexato , Farmacologia , Fenantrenos , Farmacologia , Receptor Notch3 , Receptor Notch4 , Receptores Notch , Metabolismo , Insuficiência Respiratória , Tratamento Farmacológico , Proteínas Serrate-Jagged
19.
Artigo em Chinês | WPRIM | ID: wpr-815451

RESUMO

OBJECTIVE@#To observe the changes of pulmonary function and Notch signaling pathway of lung tissues in adjuvant-induced arthritis rats, and to investigate the mechanism of reduced lung function.@*METHODS@#A total of 30 rats were randomly divided into a normal group and a model group. Rats in the model group were induced to establish the adjuvant arthritis AA model by intradermally injecting 0.1 mL Freund's complete adjuvant into the right paw. After 30 days, we observed the paw edema volume, arthritis index, pulmonary function, histomorphology, and Notch receptor/ligand of the lung tissue.@*RESULTS@#Compared with the normal group, the paw edema volume, arthritis index, average expiratory flow within 0.3 s (FEV0.3/FVC), and the level of Notch3, Notch4 and Jagged2 of the lung tissue in the model group was significantly increased, while maximum expiratory flow at 50% of vital capacity (FEF50), maximum expiratory flow at 75% of vital capacity (FEF75), forced expiratory flow (PEF) and the expression of Notch1 of Jagged1 and Delta1 in the lung were significantly decreased (P<0.05, P<0.01). There were significant positive correlations between FEV0.3/FVC and Notch4. FEV0.3/FVC, FEF25, FEF50 and Notch3, Delta1 were negatively correlated, respectively (P<0.05, P<0.01).@*CONCLUSION@#While arthritis occurs in AA rats, pulmonary function declines and significantly correlates with the expression of Notch receptor/ligand. The deposition of immune complex in the lung after the injection of CFA activates the Notch signaling pathway, and results in further decline of pulmonary function by signaling cascades.


Assuntos
Animais , Ratos , Artrite Experimental , Metabolismo , Proteínas de Ligação ao Cálcio , Metabolismo , Adjuvante de Freund , Peptídeos e Proteínas de Sinalização Intercelular , Metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Metabolismo , Proteína Jagged-1 , Pulmão , Metabolismo , Patologia , Proteínas de Membrana , Metabolismo , Receptores Notch , Metabolismo , Insuficiência Respiratória , Metabolismo , Proteínas Serrate-Jagged , Transdução de Sinais , Capacidade Vital
20.
Artigo em Chinês | WPRIM | ID: wpr-312775

RESUMO

<p><b>OBJECTIVE</b>To explore the mechanism of Astragalus polysaccharides (APS) for improving the cardiac function of Sjogren's syndrome (SS) model rats based on Keapl-Nrf2/ARE signaling pathway.</p><p><b>METHODS</b>Totally 48 male Wistar rats were randomly divided into four groups by random digit table, i.e., the blank control group,the model control group,the APS group, and the hydroxychloroquine group, 12 in each group. Except those in the blank control group, 0. 1 mL mixed antigen protein of sufficiently emulsified Freund's complete adjuvant and submandibular gland protein was injected from two feet plantar to induce SS model. The intervention was started from 19th day after inflammation induction. Equal volume of normal saline was given to rats in the blank control group (1 mL/100 g), APS was administered to those in the APS group (1 mg/100 g), and hydroxychloroquine (0.03 125 g/kg) was administered to those in the hydroxychloroquine group. All rats were intervened once per day for 30 consecutive days. Changes of rats' body mass and drinking water quantity, submandibular gland index, spleen index, histological changes of glands were observed. Changes of the heart function were monitored using invasive hemodynamics. Serum reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), tumor necrosis factor alpha (TNF-alpha), and interleukin-35 (IL-35)were detected using ELISA method. The pathological changes were observed using HE staining. The protein expression of ROS, reactive nitrogen species (RNS), glutathione (GSH), and thioredoxin (TRX) were observed by immunohistochemical staining. The mRNA expression of Keap1, Nrf2, and ARE was detected using real time fluorescent quantitative PCR. The protein expression levels of gamma-glutamic acid and a half long glycine synthetase (gamma-GCS) and heme oxygenase 1 (HO-1) in the myocardial tissue were determined by Western blot method. Results Compared with the blank control group, the quantity of drinking water, submandibular gland index, spleen index, heart rate (HR), cardiac index (HI), left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVEDP), MDA, ROS, TNF-alpha, ROS protein expression, RNS protein expression, Keap 1 mRNA expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1 protein expression, and gamma-GCS protein expression significantly increased (P <0.01); body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH, and TRX significantly decreased (P <0.01) in the model group. Compared with the model group, the quantity of drinking water, submandibular gland index, spleen index, LVEDP, MDA, ROS, TNF-alpha, ROS protein expression, RNS protein expression, Keap1 mRNA expression, Maf mRNA expression, Nfr2 mRNA expression, and HO-1 protein expression, and gamma-GCS protein expression significantly decreased (P<0.05); body mass, +/-dp/dtmax, SOD, TAC, IL-35, GSH protein expression, and TRX protein expression significantly increased (P < 0.05, P <0.01) in the AR group and the hydroxychloroquine group. In the hydroxychloroquine group HR increased (P <0.05). In the AR group HR and LVSP decreased (P <0. 05, P <0. 01). Compared with the hydroxychloroquine group, HR, LVEDP, - dp/dtmax, y-GCS protein expression significantly decreased (P <0. 05, P <0. 01); SOD, TAC, GSH, TRX, HO-1 protein expression increased (P <0.01 )in the AR group. HI was positively correlated with ROS (P <0. 05). LVSP and LVEDP were positively correlated with Keap1 -Nrf2/ARE signaling pathways (P <0. 01) , and negatively correlated with TAC (P <0. 05, P <0. 01 ). +/-dp/dtmax was negatively correlated with Keap1-Nrf2/ARE signaling pathways(P <0.05), and positively correlated with TNF alpha (P <0. 05).</p><p><b>CONCLUSIONS</b>Declined heart function exists in SS rats. The mechamechanism of APS for improving the heart function might be closely correlated with activating Keap1-Nrf2/ARE signaling pathway.</p>


Assuntos
Animais , Masculino , Ratos , Astrágalo , Western Blotting , Hidrolases de Éster Carboxílico , Metabolismo , Heme Oxigenase-1 , Metabolismo , Hidroxicloroquina , Malondialdeído , Metabolismo , Miocárdio , Fator 2 Relacionado a NF-E2 , Metabolismo , Extratos Vegetais , Usos Terapêuticos , Polissacarídeos , Metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio , Metabolismo , Transdução de Sinais , Síndrome de Sjogren , Glândula Submandibular , Superóxido Dismutase , Metabolismo , Tiorredoxinas , Metabolismo , Fator de Necrose Tumoral alfa , Metabolismo
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