RESUMO
Objective@#To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (TNF-RII) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents. @*Methods@#PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for TNF-RII rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods. @*Results@#G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD. @*Conclusion@#These results suggest reciprocal actions of TNF-RII rs1061622 with other factors on PTSD severity, interplays of TNF-RII rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of TNF-RII rs1061622 after experiencing traumatic events.
RESUMO
Objective:To establish a model of cervical spondylosis of vertebral artery type (CSA) in rats by mixed modeling method, and observe the intervention effect of Panlongqi tablet (PLQT) on CSA rats. Method:SD rats were divided into a normal control group, a model group, low- (0.16 g·kg<sup>-1</sup>), medium- (0.32 g·kg<sup>-1</sup>), and high-dose (0.64 g·kg<sup>-1</sup>) PLQT groups, and a Jingfukang granule (JFK, 1.35 g·kg<sup>-1</sup>) group. The rats were treated correspondingly 24 hours after modeling for eight weeks, and those in the normal control group received an equal volume of normal saline by gavage. The limb movement was tested by the inclined plate assay, vertebral artery flow volume by multi-mode high-frequency sound wave for small animals, and microcirculatory blood flow in the pia mater by the laser Doppler. The imaging of the cervical spine was recorded and scored by X-ray micro-computed tomography (Micro CT). Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of endothelin-1 (ET-1), nitric oxide (NO), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI). Result:Compared with the normal control group, the model group showed decreased limb movement, vertebral artery flow volume, and microcirculatory blood flow in the pia mater, and increased imaging of the cervical spine and score (<italic>P</italic><0.05,<italic>P</italic><0.01). PLQT could dose-dependently improve the motor function, increase the vertebral artery flow volume and microcirculatory blood flow in the pia mater, and reduce the degree and score of imaging of the cervical spine in CSA rats(<italic>P</italic><0.05,<italic>P</italic><0.01). The serum levels of NO and t-PA were decreased and those of ET-1 and PAI were increased in the model group as compared with those in the normal control group, while such changes were reversed by PLQT treatment(<italic>P</italic><0.05,<italic>P</italic><0.01). Conclusion:PLQT can enhance the limb movement, promote the vertebral artery flow volume and microcirculatory blood flow in the pia mater, improve the degree of imaging of the cervical spine, regulate the vasomotor function, and improve the coagulation and fibrinolysis system of CSA rats, which shows good potential for the treatment of CSA.
RESUMO
Objective:To observe the effect of Tongluo Shenggu capsule (TLSGC) on glucocorticoid-induced vascular endothelial cell functional damage, and to preliminally explore the mechanism of action through MEK-ERK signaling pathway. Method:The blood vessel of aorta rings of normal SD rats were induced <italic>in vitro</italic> intervention with methylprednisolone sodium succinate (MPS, 0.04 g·L<sup>-1</sup>) and/or vascular endothelial growth factor (VEGF, 20 μg·L<sup>-1</sup>), and were treated with TLSGC(12.5, 25, 50 μg·L<sup>-1</sup>) continuously for 5 days to observe the number, length and area of microvascular ring buds.In addition, human umbilical vein endothelial cells (HUVEC) induced by VEGF(20 μg·L<sup>-1</sup>) were added into MPS(0.04 g·L<sup>-1</sup>) and TLSGC (12.5, 25, 50 μg·L<sup>-1</sup>) were added. Then, Transwell migration, Transwell invasion and lumen formation experiments were used to detect the migration, invasion and lumen formation ability of HUVEC, respectively. The content of nitric oxide(NO) in the cell supernatant was detected by nitrate reductase method, the content of endothelin 1(ET-1) in the cell supernatant was detected by dry powder method. Moreover, the protein contents of vascular endothelial growth factor receptor 2 (VEGFR2), extracellular signal-regulated kinase (ERK), phospho-extracellular signal-regulated kinase (p-ERK), mitogen extracellular kinase1(MEK) and phosphorylated mitogen extracellular kinase1(p-MEK) in the cells were determined by Western blot. Result:Compared with the normal group, MPS could significantly inhibit the number, length and area of VEGF-induced rat thoracic aortic ring microvessels, HUVEC cell migration, invasion and lumen formation ability. It could reduce NO content and increase ET-1 content. MPS could also significantly reduce the protein content of VEGF-induced VEGFR2, p-MEK and p-ERK in HUVEC(<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with the model group, TLSGC could dose-dependently increase the number, length and area of MPS-induced abnormally reduced rat thoracic aortic ring microvessels, promote MPS-induced abnormally decreased HUVEC cell migration, invasion and lumen formation ability. It could increase the protein contents of NO, VEGFR2, p-MEK and p-ERK in HUVEC, and reduce abnormally increased ET-1 content(<italic>P</italic><0.05<italic>,P</italic><0.01). Conclusion:TLSGC has a protective effect on the damage of angiogenesis and secretion of vascular endothelial cells induced by glucocorticoid, and the mechanism may be related to the activation of MEK/ERK signaling pathway.
RESUMO
The aim of this paper was to compare different effects of Tripterygium Glycosides Tablets from 6 different manufacturers on multiple organ injuries in rats and to explore mechanism of hepatotoxicity preliminarily from the perspective of apoptosis and oxidative stress. Rats were randomly divided into the groups normal, Zhejiang, Hunan, Hubei, Shanghai, Jiangsu and Fujian(7 groups with 16 rats in each group, sex in half). Rats were given Tripterygium Glycosides Tablets at 144 mg·kg~(-1)·d~(-1)(16 times the clinical equivalent dose) once a day according to its corresponding group like rats in Zhejiang group was given Tripterygium Glycosides Tablets from Zhejiang manufactures continuously for 20 days with the life and death situation of mice to be observed, then rats were executed to detect various indicators. RESULTS:: showed that 8 female rats in Zhejiang group died after 15 days of administration, the serum NEUT of rats in Hubei, Fujian and Shanghai groups was significantly lower than that of normal rats. The serum AST, ALT and/or TBiL levels were increased in all rats, and serum BUN and/or CRE levels of rats were also increased in Hunan, Hubei, Fujian and Shanghai groups. In dosage groups, testicular and ovarian coefficients of rats were reduced, the number of sperm were significant decreased while the rate of sperm malformation increased and sperm dynamics parameters of normal, especially in Jiangsu and Zhejiang groups. Liver histopathology and apoptosis of liver cells were observed in dosage groups, especially in Jiangsu and Hubei groups. In liver, Nrf2, HO-1 and Bcl-2 were inhibited and the protein expression level of Bax were increased simultaneously in dosage groups. These results showed that all Tripterygium Glycosides Tablets from 6 manufacturers could lead to chronic multiple organ injuries with disparate specialties in rats, and Jiangsu and Zhejiang groups were more toxic. It could be the mechanism promoting mitochondrial mediated Bax/Bcl-2 cell apoptosis signaling pathway and negatively regulating Nrf2/HO-1 oxidative stress signaling pathway that Tripterygium Glycosides Tablets from 6 different manufacturers resulted in chronic liver injury, the results above were for reference only in subsequent study.
Assuntos
Animais , Feminino , Masculino , Ratos , Apoptose , China , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Estresse Oxidativo , Distribuição Aleatória , Transdução de Sinais , Comprimidos , Tripterygium/químicaRESUMO
To systematically evaluate the adverse drug reaction(ADR) of Tripterygium Glycosides Tablets(TGT) in the treatment of rheumatoid arthritis(RA). Four Chinese databases(CNKI, VIP, WanFang, SinoMed) and three English databases(Cochrane Library, EMbase, PubMed), from the time of database establishing to August 2019, were systematically retrieved to collect literature on the treatment of all types of RA with TG. Screening literature and extracting data according to inclusion and exclusion criteria. All studies were assessed by using internationally recognized methodological quality assessment tools or reporting quality evaluation criteria, with data being extracted and Meta-analyzed. There were 79 studies included, randomized controlled trials(RCT) containing TGT in the treatment group, non-randomized controlled trials(non-RCT), case series, case reports, and RCT containing TGT only in the control group were covered. There were in the control group; 765 ADR of 2 214 patients in 30 RCT(treatment group given TGT), 11 non-RCT and 7 case reports. The results of Meta-analysis of these 48 literatures showed that the overall incidence of ADRs was 0.23(95%CI[0.22,0.24]); ADR mainly occured in the reproductive, gastrointestinal, skin and accessories, blood, hepatobiliary system damage and the incidence of ADR in systems mentioned about respectively were 0.14(95%CI[0.12,0.17]),0.07(95%CI[0.06,0.08]),0.06(95%CI[0.04,0.07]),0.04(95%CI[0.03,0.05]),0.04(95%CI[0.03,0.05]). Further subgroup analysis results showed that the incidence of total ADR, especially the gastrointestinal, reproductive and cutaneous ADR of patients with treatment alone was higher than that in those paients with MTX or MTX+LEF therapy; The incidence of ADR, especially the gastrointestinal ADR, was also positively correlated with daily dose and course of treatment, while the incidence of different systems ADR was also correlated with different drug manufacturers, for instance, damage on the female reproductive system occurs most frequently in Hunan manufacture TGT administration, same as the damage on skin and accessories induced by TGT from Jiangsu manufacture. Above all, The clinical treatment of TGT for RA will cause multi-system ADR, with the highest incidence in the reproductive system, followed by the gastrointestinal system, which is closely related to the way of medication(monotherapy), daily dose, course of medication and drug manufacturer. Therefore, it is recommended that, in the treatment of RA, using TGT in combination, low dose or short-course medication, take measures to protect the reproductive system, stomach and liver, and paying attention to the drug manufacturer as well response of patients during administration should be valued to avoid ADRs to the maximum possibility.
Assuntos
Humanos , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Glicosídeos/uso terapêutico , Ensaios Clínicos Controlados não Aleatórios como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Comprimidos , Tripterygium/químicaRESUMO
The aim was to observe the analgesic effect of Fengshi Qutong Capsules(FSQTC) on chronic inflammatory pain in mice, and investigate its effect on p-ERK/COX-2 signal molecular activity. A model of chronic inflammatory pain was induced in mice by complete Freund's adjuvant(CFA). The mice were divided into normal control group, model group, model+FSQTC 0.3, 0.6 and 1.2 g·kg~(-1 )groups, model+positive control drug ibuprofen(IBP, 0.34 mg·kg~(-1)·d~(-1)) group, and normal control+ FSQTC 1.2 g·kg~(-1)group. FSQTC or IBP was given once a day by oral administration. Standard Von Frey fiber was used to evaluate the mechanical pain threshold, and the acetone stimulation was used to induce inflammatory plantar and observe the cold pain reaction scores. The mechanical pain threshold and cold pain reaction scores were observed before administration and 1, 2, 3, 4, 6 h after administration on the first day, as well as 3 h after administration on the 3 rd to 7 th day. The protein levels of PGE_2, COXs-1,2 and p-ERK in the spinal cord of the inflammatory foot and lumbar 4-5 were detected by enzyme-linked immunosorbent assay, Western blot, immunohistochemistry and immunofluorescence. The results showed that the mechanical pain threshold of the model group decreased and the cold pain reaction score increased as compared with the normal group. FSQTC application could dose-dependently increase the mechanical pain threshold and decrease the cold pain reaction score. The effect lasted for 6 h, most significant at 3 h. The effect of ibuprofen was similar to that of the 0.6 g·kg~(-1) dose group. In addition, FSQTC could reduce the abnormally increased protein content of PGE_2, COX-2 and p-ERK in the inflammatory foot and/or spinal cord of the model group, and the effect was most significant in middle and high dose groups. However, it had no effect on COX-1 in the inflammatory foot and spinal cord of mice. The results suggest that FSQTC has ob-vious analgesic effect on chronic inflammatory pain in mice, which may be related to inhibition of p-ERK/COX-2 signaling pathway.
Assuntos
Animais , Camundongos , Analgésicos/uso terapêutico , Cápsulas , Medicamentos de Ervas Chinesas/uso terapêutico , Adjuvante de Freund , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Ratos Sprague-DawleyRESUMO
Objective:To observe the analgesic effect of Panlongqi tablet(PLQT) on rats with chronic inflammatory pain, and to explore mechanism of the action preliminarily from the perspective of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)and mitogen-activated protein kinase(MAPKs) signaling pathways. Method:Rats were induced to establish model of chronic inflammatory pain by complete Freund adjuvant(CFA), which was divided into normal group, model group, the PLQT 0.16,0.32,0.64 g·kg-1 group, and the ibuprofen 0.05 g·kg-1 group(also positive group), give the medicine once a day by gavage. Standard Von Frey fiber was used to evaluated the mechanical pain threshold, acetone was used to stimulated rats inflammatory foot to get the cold-induced response score, with the mechanical pain threshold and cold-induced response score to be observed at 1, 2, 3, 4 and 6 h before and after administration on day 1, and at 4 h after administration on day 3-7. The content of PGE2, IL-1, TNF-α in serum, inflammatory foot and 4-5 lumbar spinal cord was detected by enzyme-linked immunosorbent assay(ELISA). The protein level of MAPKs (p-p38, p-ERK, p-JNK) in lumbar spinal cord 4-5 was detected by Western blot. The expression of NF-κB p65 in the lumbar spinal cord was detected by IFA. Result:Model group had lower mechanical pain threshold and higher cold-induced response score than these in normal group(P<0.01), while the mechanical pain threshold and cold-induce response score of the model rats were dose-dependent better regulated after administration of PLQT 0.16, 0.32, 0.64 g·kg-1·d-1(P<0.05,P<0.01), these effect lasted 6 h, of which PLQT groups get the most significant effect on 4 h, however the effect of IBP was similar to that of PLQT medium dose group. In addition, PLQT reduced the abnormal increase of PGE2, IL-1 and TNF-α contents in serum, inflammatory foot and spinal cord of rats in model group, decreased the protein phosphorylation levels of ERK and JNK in spinal cord, and decreased the protein expression of NF-κB p65, that was significant in the PLQT high-dose group(P<0.01). Conclusion:PLQT had significant analgesic effect on chronic inflammatory pain model rats, which may be related to the inhibition of NF-κB and MAPKs signaling pathways in spinal cord.
RESUMO
The aim of this paper was to compare the performance of acute liver injury in mice induced by Tripterygium Glycosides Tablets from 6 different manufacturers,and to explore the toxicity mechanism from the perspective of oxidative stress and apoptosis preliminarily. Male or female mice were randomly divided into normal group,Zhejiang group,Hunan group,Hubei group,Shanghai group,Jiangsu group and Fujian group. Mice in Tripgerygium Glycosides Tablets groups were given 16 times the clinical equivalent dose( 300 mg·kg-1) Tripgerygium Glycosides Tablets by oral administration for one time,mice were executed in 24 h after lavaged.Then the visceral brain coefficient of the organ was calculated. Histopathological changes of liver were observed by hematoxylin-eosin staining. Td T-mediated d UTP nick-end labeling was used to detect the apoptosis of the liver cells and the protein content of oxidative stress related factors in liver homogenate. Nuclear transcription factor E2-related factor( Nrf2) and heme oxygenase-1( HO-1) as well as mitochondrial mediated apoptosis-related protein expression levels of Bax and Bcl-2 in hepatic tissue were measured by Western blot.Within 24 hours of administration,6 male mice in Jiangsu group and 2 female mice in Zhejiang group were dying; compared with normal ones,liver coefficients of mice in Zhejiang,Shanghai,Jiangsu and Hunan groups were significantly increased,thymus coefficients in the first two groups were significantly reduced,as well as the lung coefficients of Fujian group mice,the rest was normal. In addition to Hubei group,serum AST,ALT or ALP levels of mice were increased,while TBi L were not being affected. Histopathological changes and apoptosis of liver cells were observed in all mice,and the degree of severity was ranked as Jiangsu,Zhejiang,Shanghai,Hunan,Hubei and Fujian group. All Tripterygium Glycosides Tablets increased the MDA and reduced the content of T-SOD,CAT or GSH in liver tissue while inhibited Nrf2,HO-1 and Bcl-2,increased the protein expression level of Bax( except Hunan group). Tripgerygium Glycosides Tablets from 6 manufacturers all resulted in liver function damage and liver histopathological changes,especially in Jiangsu,Hubei and Fujian,and the mechanism may related to inhibit Nrf2/HO-1 oxidative stress pathway and activate Bax/Bcl-2 apoptosis pathway to mediate lipid peroxidation and induce liver cell apoptosis. Triptolide A may be one of the main toxic components of Tripgerygium Glycosides Tablets that causing drug-induced liver injury. This study was conducted on normal mice with super dose medication,so the relevant results are for reference only.
Assuntos
Animais , Feminino , Masculino , Camundongos , Apoptose , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Toxicidade , Glicosídeos , Toxicidade , Heme Oxigenase-1 , Metabolismo , Peroxidação de Lipídeos , Fígado , Proteínas de Membrana , Metabolismo , Fator 2 Relacionado a NF-E2 , Metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2 , Metabolismo , Distribuição Aleatória , Comprimidos , Tripterygium , Toxicidade , Proteína X Associada a bcl-2 , MetabolismoRESUMO
To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 μg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.