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Myocardial injury and ensuing fibrotic alterations impair normal heart architecture and cause cardiac dysfunction. Oxidative stress has been recognized as a key player in the pathogenesis of cardiac injury and progression of cardiac dysfunction, and promoting fibrosis. In the current study we investigated whether luteolin-7-diglucuronide (L7DG), a naturally occurring antioxidant found in edible plants, could attenuate isoproterenol (ISO)-induced myocardial injury and fibrosis in mice and the underlying mechanisms. Myocardial injury and fibrosis were induced in mice via injection of ISO (5 mg·kg-1·d-1, ip) for 5 or 10 d. Two treatment regimens (pretreatment and posttreatment) were employed to administer L7DG (5-40 mg·kg-1·d-1, ip) into the mice. After the mice were euthanized, morphological examinations of heart sections revealed that both L7DG pretreatment and posttreatment regimens significantly attenuated ISO-induced myocardial injury and fibrosis. But the pretreatment regimen caused better protection against ISO-induced myocardial fibrosis than the posttreatment regimen. Furthermore, L7DG pretreatment blocked ISO-stimulated expression of the genes (Cyba, Cybb, Ncf1, Ncf4 and Rac2) encoding the enzymatic subunits of NADPH oxidase, which was the primary source of oxidant production in mammalian cells. Moreover, L7DG pretreatment significantly suppressed ISO-stimulated expression of collagen genes Col1a1, Col1a2, Col3a1, and Col12a1 and non-collagen extracellular matrix genes fibrillin-1, elastin, collagen triple helix repeat containing 1 and connective tissue growth factor. In addition, L7DG pretreatment almost reversed ISO-altered expression of microRNAs that were crosstalking with TGFß-mediated fibrosis, including miR-29c-3p, miR-29c-5p, miR-30c-3p, miR-30c-5p and miR-21. The current study demonstrated for the first time that L7DG is pharmacologically effective in protecting the heart against developing ISO-induced injury and fibrosis, justifying further evaluation of L7DG as a cardioprotective agent to treat related cardiovascular diseases.
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Antioxidantes/farmacologia , Cardiomiopatias/tratamento farmacológico , Cardiotônicos/farmacologia , Glucuronatos/farmacologia , Luteolina/farmacologia , Miocárdio/patologia , Animais , Antioxidantes/uso terapêutico , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/patologia , Cardiotônicos/uso terapêutico , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Fibrose/induzido quimicamente , Fibrose/patologia , Fibrose/prevenção & controle , Glucuronatos/isolamento & purificação , Glucuronatos/uso terapêutico , Isoproterenol , Lamiaceae/química , Luteolina/isolamento & purificação , Luteolina/uso terapêutico , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Necrose/induzido quimicamente , Necrose/tratamento farmacológico , Necrose/patologiaRESUMO
BACKGROUND: Cirrhosis is associated with angiogenesis and disruption of hepatic vascular architecture. Yiguanjian (YGJ) decoction, a prescription from traditional Chinese medicine, is widely used for treating liver diseases. We studied whether YGJ or its ingredients (iYGJ) had an anti-angiogenic effect and explored possible mechanisms underlying this process. METHODS: Cirrhosis was induced with carbon tetrachloride (CCl4) (ip) in C57BL/6 mice for 6 weeks. From week 4 to week 6, cirrhotic mice were randomly divided into four groups: sorafenib-treated, YGJ-treated and iYGJ-treated mice and placebo. Serum biochemistries, hydroxyproline (Hyp) content and histopathological changes of hepatic tissues were measured as were α-smooth muscle actin (α-SMA), collagen I, CD31, vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 2 and hypoxia-inducible factor (HIF)-1α. RESULTS: Both YGJ and iYGJ improved serum biochemistries. Changes of histopathology showed that YGJ and iYGJ reduced hepatic tissue necroinflammatory and collagen fiber deposition in cirrhosis mice. Compared to the CCl4 treated animals, Hyp, α-SMA, collagen I, CD31, VEGF, VEGFR, and HIF-1α expression decreased in YGJ and iYGJ groups. CONCLUSIONS: YGJ and iYGJ inhibited liver angiogenesis in cirrhotic mice treated with CCl4 by inhibiting the HIF-1α/VEGF signaling pathway, suggesting that anti-angiogenic effects of YGJ and iYGJ are associated with improving the hepatic hypoxic microenvironment.
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Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática Experimental/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Actinas , Inibidores da Angiogênese/uso terapêutico , Animais , Tetracloreto de Carbono , Colágeno/efeitos adversos , Hidroxiprolina/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática Experimental/metabolismo , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Emerging VR applications have revolutionized user experiences by immersing individuals in digitally crafted environments. However, fully immersive experiences introduce new challenges, notably the risk of physical hazards when users are unaware of their surroundings. Existing solutions, including guardian spaces and locomotion systems, present trade-offs that either disrupt the immersive experience or risk inducing motion sickness. To address these challenges, we propose a novel approach that dynamically rearranges VR scenes according to users' physical spaces, seamlessly embedding physical constraints and interaction tasks into the virtual environment. We design a computational model to optimize the rearranged scene through a cost function, ensuring collision-free interactions while maintaining visual fidelity and the goal of interaction tasks. The experiments demonstrate improvements in user experience and safety, presenting an innovative solution to harmonize physical and virtual environments in VR applications.
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Objective: The purpose of this study was to evaluate the protective effect of Shengmai Zhenwu decoction on patients with chronic heart failure (CHF) based on the levels of soluble interleukin 1 receptor-like 1 (ST2). Methods: We included a total of 80 outpatients and inpatients with CHF who were undergoing treatment at the Shanghai Municipal Hospital of Traditional Chinese Medicine between March 2020 and March 2022. We randomly divided them into the observation group (n = 40) and the control group (n = 40). Patients in the control group received treatments as per conventional Western medicine, while those in the observation group were treated with the Shengmai Zhenwu decoction in conjunction with Western medicine for eight consecutive weeks. We then compared the pre- and post-treatment levels of ST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) of the patients in the two groups. Results: There were no significant differences in the pre-treatment levels of ST2 and NT-proBNP indexes between the two groups (P > 0.05), while the post-treatment comparison between the two groups in terms of ST2 and NT-proBNP levels suggested that the effect in the observation group was better, with statistical significance (P < 0.05). Conclusion: Shengmai Zhenwu decoction was beneficial in patients with CHF, suggesting that it could be a promising and effective method for the treatment of CHF.
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OBJECTIVE: To investigate the effects of three classical anti-jaundice formulas Yinchenhao Decoction (YCHD). Yinchen Wuling San (YCWLS) and Zhizi Baipi Decoction (ZZBPD) on liver fibrosis induced by dimethylnitrosamine (DMN) in rats and explore the formula-syndrome relationship. METHODS: Forty-eight rats were weighted, and divided into five groups: normal control, DMN, YCHD, YCWLS and ZZBPD groups using stratified random method. Liver fibrosis in rats was induced by intraperitoneal injection of DMN for 4 weeks at the dosage 10 mg/kg body weight, once per day for 3 consecutive days in each week. Each groups was gavaged with distilled water (control or model group), YCHD, YCWLS and ZZBPD respectively in the last 2-week modeling period. At the end of the 4th week, rats were sacrificed and their blood sample and liver tissue were taken for detecting pathology and analyzing of hydroxyproline (Hyp) and liver function. RESULTS: Compared with the normal control group, DMN model group showed liver damage and liver fibrosis with remarkably increased Hyp content (P<0.01) and abnormal liver function (P<0.01). Liver fibrosis induced by DMN in rats was improved by administration of YCHD. Compared with DMN model group, content of Hyp was decreased remarkably (P<0.01) and liver function and hepatic histology were improved significantly after 2 weeks of YCHD treatment (P<0.05 or P<0.01)., and content of hepatic Hyp was decreased in the ZZBPD groups. Comparison of various parameters between groups showed that content of serum total bilirubin was decreased significantly in the YCWLS group (P<0.01), and content of hepatic Hyp was decreased in the ZZBPD group. CONCLUSION: Efficacy of YCHD in inhibition of liver fibrosis induced by DMN in rats is far better than YCWLS and ZZBPD. The pathogenesis of the liver fibrosis induced by DMN is mainly damp-heat. In addition, both damp and heat pathogenic factors play very important role in this model. The syndrome is highly correlated with the prescription YCHD.
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Dimetilnitrosamina/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/tratamento farmacológico , Fitoterapia , Animais , Hidroxiprolina/análise , Fígado/patologia , Cirrose Hepática Experimental/patologia , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To explore the intervention effects of Xiaopi Pill (XPW), a compound traditional Chinese herbal medicine, on the development progress of dimethylnitrosamine (DMN)-induced liver fibrosis in rats. METHODS: Liver fibrosis model was established by intraperitoneal injection of 0.5% DMN 2 mL/kg thrice a week for 4 weeks. Rats were divided into control group given saline and treatment group given XPW during the 3rd week of DMN injections. Rats were sacrificed at the end of the experiment, and then liver histological changes, liver function and mRNA expression of the liver fibrosis-associated markers were observed. RESULTS: (1) At the end of the 2nd and 4th weeks of DMN injection, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) increased significantly in rats (P<0.01 or P<0.05); content of total bilirubin (TBil) increased significantly compared with the normal group until the end of the 4th week (P<0.05); compared with the model group after 4 weeks of DMN injection, the serum levels of ALT, AST, ALP and TBil were decreased remarkably in the XPW-treated group (P<0.01 or P<0.05). (2) The hepatic inflammation and collagen deposition in hepatic tissues increased by different degrees in experimental rats. Parts of pathological changes in the rat liver were found at the end of the 4th week, including a complete round structure of false flocculus round, meantime, the hydroxyproline content of hepatic tissue was increased significantly at the end of the 2nd and 4th weeks (P<0.05). Compared with the 4-week model group, the hepatic inflammation, collagen deposition and hydroxyproline content in hepatic tissues were alleviated dramatically (P<0.05). (3) Compared with the normal and 2nd week groups, protein expression of alpha-smooth muscle actin (α-SMA) was gradually increased, and that of the 4th week group were aggrandized significantly (P<0.01). Compared with the normal group, the mRNA expression of α-SMA, transforming growth factor-ß1 (TGF-ß1), tissue inhibitor of metalloproteinase-1 (TIMP-1), and heme oxygenase-1 (HO-1) was gradually increased. Further changes in above-mentioned abnormalities were found in the model rats at the end of the 4th week (P<0.01); while compared to the 4th week group, protein and mRNA levels of α-SMA and mRNA levels of TGF-ß1, TIMP-1, and HO-1 were decreased significantly in the XPW group (P<0.01 or P<0.05). CONCLUSION: Progressive DMN-induced liver fibrosis in rats can be suppressed by XPW; the mechanism may be associated with inhibition of the activated hepatic stellate cells.
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Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática Experimental/patologia , Fígado/patologia , Animais , Dimetilnitrosamina/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Hidroxiprolina/metabolismo , Fígado/metabolismo , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
[This corrects the article on p. 2068 in vol. 10, PMID: 30093944.].
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Correction for 'Highly porous and elastic aerogel based on ultralong hydroxyapatite nanowires for high-performance bone regeneration and neovascularization' by Gao-Jian Huang et al., J. Mater. Chem. B, 2021, 9, 1277-1287, DOI: 10.1039/D0TB02288H.
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Hydroxyapatite (HAP) is promising for the clinical treatment of bone defects because of its excellent biocompatibility and osteo-conductivity. However, highly porous HAP scaffolds usually exhibit high brittleness and poor mechanical properties, thus organic constituents are usually added to form composite materials. In this work, a highly porous and elastic aerogel made from ultralong HAP nanowires with ultrahigh porosity (â¼98.5%), excellent elasticity and suitable porous structure is prepared as the high-performance scaffold for bone defect repair. The highly porous structure of the as-prepared aerogel is beneficial to bone ingrowth and matter/fluid transfer, and the high elasticity can ensure the structural integrity of the scaffold during bone regeneration. Therefore, the HAP nanowire aerogel scaffold can promote the adhesion, proliferation and migration of rat bone marrow derived mesenchymal stem cells (rBMSCs), and elevate the protein expression of osteogenesis and angiogenesis related genes. The in vivo experimental results demonstrate that the HAP nanowire aerogel scaffold is favorable for the ingrowth of new bone and blood vessels, and thus can greatly accelerate bone regeneration and neovascularization. The as-prepared HAP nanowire aerogel scaffold shows promising potential for biomedical applications such as bone defect repair.
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Materiais Biocompatíveis/farmacologia , Regeneração Óssea/efeitos dos fármacos , Bandagens Compressivas , Durapatita/farmacologia , Neovascularização Patológica/tratamento farmacológico , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Durapatita/síntese química , Durapatita/química , Masculino , Teste de Materiais , Neovascularização Patológica/patologia , Tamanho da Partícula , Porosidade , Ratos , Ratos Sprague-Dawley , Propriedades de SuperfícieRESUMO
The functionality of a workspace is one of the most important considerations in both virtual world design and interior design. To offer appropriate functionality to the user, designers usually take some general rules into account, e.g., general workflow and average stature of users, which are summarized from the population statistics. Yet, such general rules cannot reflect the personal preferences of a single individual, which vary from person to person. In this paper, we intend to optimize a functional workspace according to the personal preferences of the specific individual who will use it. We come up with an approach to learn the individual's personal preferences from his activities while using a virtual version of the workspace via virtual reality devices. Then, we construct a cost function, which incorporates personal preferences, spatial constraints, pose assessments, and visual field. At last, the cost function is optimized to achieve an optimal layout. To evaluate the approach, we experimented with different settings. The results of the user study show that the workspaces updated in this way better fit the users.
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Ergonomia/métodos , Realidade Virtual , Local de Trabalho , Algoritmos , Gráficos por Computador , Simulação por Computador , Ergonomia/estatística & dados numéricos , Humanos , Decoração de Interiores e Mobiliário/métodos , Decoração de Interiores e Mobiliário/estatística & dados numéricos , Postura , Análise e Desempenho de Tarefas , Interface Usuário-ComputadorRESUMO
Statins and therapeutic ultrasound (TUS) have been shown to ameliorate angiogenesis on ischemic hindlimb animals and promote human umbilical vein endothelial cells (HUVECs) tube formation and proliferation. Here, we evaluate the therapeutic effect of TUS in combination with atorvastatin (Ator) therapy on angiogenesis in hindlimb ischemia and HUVECs. After subjecting excision of the left femoral artery, all mice were randomly distributed to one of four groups: Control; Ator treated mice (Ator); TUS treated mice (TUS); and Ator plus TUS treated mice (Ator+TUS). At day 14 post-surgery, the Ator plus TUS treatment cohort had the greatest blood perfusion, accompanied by elevated capillary density. In vitro, Ator plus TUS augmented tube formation, migration and proliferative capacities of HUVECs. Additionally, the united administration upregulated expression of angiogenic factors phosphorylated Akt (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor (VEGF), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. Our data indicated that the united administration could significantly enhance ischemia-mediated angiogenesis and exert a protective effect against ischemic/hypoxia induced damage among HUVECs through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway.
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[This corrects the article on p. 2068 in vol. 10, PMID: 30093944.].
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Nanostructured calcium phosphate (CaP) and magnesium phosphate (MgP) are promising for the application as the nanocarriers in drug delivery. However, the difference between CaP and MgP nanocarriers in drug delivery is rarely investigated. In this work, we comparatively investigated nanostructured CaP, MgP and calcium magnesium phosphate (CMP) for the delivery of SRT1720, which is a silent information regulator (SIRT1) specific activator with pro-angiogenic and anti-aging properties in response to hydrogen peroxide (H2O2)-induced endothelial senescence. The protection of SRT1720-loaded CaP nanospheres, MgP nanosheets and CMP microspheres on the H2O2-induced senescent endothelium was examined by using human umbilical vein endothelial cells (HUVECs), demonstrating the improved cell viability, anti-aging, tube formation and migration. In addition, the SRT1720-loaded CaP nanospheres, MgP nanosheets and CMP microspheres can rescue the impaired angiogenic potential of HUVECs via activation of Akt/eNOS/VEGF pathway. The SRT1720-loaded MgP nanosheets and CMP microspheres have a similar protective effect compared with the pure SRT1720, while the SRT1720-loaded CaP nanospheres decrease the protective capability of SRT1720. These results lead us to figure out both MgP nanosheets and CMP microspheres are suitable and effective delivery for SRT1720 and this system can be further applied in vivo treatment.
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BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has become an emerging treatment modality for acute type B aortic dissection (TBAD) patients in recent years. The risk factors and impacts of acute kidney injury (AKI) after percutaneous TEVAR, however, have not been widely established. METHODS: We retrospectively studied the clinical records of 305 consecutive patients who admitted to our institution and had TEVAR for TBAD between December 2009 and June 2013. The patients were routinely monitored for their renal functions preoperatively until 7 days after TEVAR. The Kidney Disease Improving Global Guidelines (KDIGO) criteria were used for AKI. RESULTS: Of the total 305 consecutive patients, 84 (27.5%) developed AKI after TEVAR, comprising 66 (21.6%) patients in KDIGO stage 1, 6 (2.0%) patients in stage 2 and 12 (3.9%) patients in stage 3. From the logistic regression analysis, systolic blood pressure (SBP) on admission >140 mmHg (odds ratio [OR], 2.288; 95% CI, 1.319-3.969) and supra-aortic branches graft bypass hybrid surgery (OR, 3.228; 95% CI, 1.526-6.831) were independent risk factors for AKI after TEVAR. Local anesthesia tended to be a protective factor (OR, 0.563; 95% CI, 0.316-1.001). The preoperative renal function, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or statin administration, volume of contrast agent, range of TBAD and false lumen involving renal artery were not associated with post-operation AKI. The in-hospital mortality and major adverse events were markedly increased with the occurrence of AKI (7.1% vs 0.9%, P=0.006; 14.3% vs 3.2%, P<0.001, respectively). CONCLUSIONS: TEVAR for TBAD has a high incidence of AKI, which is associated with worse in-hospital outcomes. SBP on admission and supra-aortic branches graft bypass hybrid surgery were the most significant risk factors. Renopreventive measures should be considered in high-risk patients.
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OBJECTIVE: To realize propensity score matching in PS Matching module of SPSS and interpret the analysis results. METHODS: The R software and plug-in that could link with the corresponding versions of SPSS and propensity score matching package were installed. A PS matching module was added in the SPSS interface, and its use was demonstrated with test data. RESULTS: Score estimation and nearest neighbor matching was achieved with the PS matching module, and the results of qualitative and quantitative statistical description and evaluation were presented in the form of a graph matching. CONCLUSION: Propensity score matching can be accomplished conveniently using SPSS software.
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Pontuação de Propensão , SoftwareRESUMO
To investigate the relation between quantitative blood flow parameters on 3-dimensional (3D) color histogram, 3D ultrasound characteristics and Ki-67 expression in breast cancer. Three-dimensional ultrasound characteristics and histological classifications of 76 breast tumors in 75 confirmed cases were analyzed. Relations of tumor volume (V), vascularization index (VI), flow index (FI) and vascularization-flow index (VFI) on 3D color histogram to Ki-67 expression were studied by statistical methods. VI and VFI measurements of tumors in positive Ki-67 expression group were obviously increased compared with the negative expression group (P<0.05). V and FI measurements of positive expression group were higher than those of the negative expression group, but the difference was not significant (P>0.05). Cases showing positive expression of Ki-67 were more likely to have lymph node metastases (P<0.05), and Ki-67 expression positively correlated with histological classification (P<0.05). However, the two groups did not show significant differences in the findings of "sun-like symptom" (P>0.05). Qualitative and quantitative 3D ultrasound characteristics correlated with positive expression of Ki-67 in breast cancer. Quantitative analysis with 3D color histogram more accurately evaluates blood supply of breast tumors, providing references for predicting biological behaviors and prognosis of breast cancer.
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ETHNOPHARMACOLOGICAL RELEVANCE: Xuefuzhuyu decoction (XFZY) is a well-known traditional Chinese herbal formulation composed of 11 herbs. It is an effective treatment for cardiovascular and chronic liver diseases. The aim of the study is to investigate the role of XFZY on angiogensis in hepatic fibrogenesis, and identify the possible mechanism. MATERIAL AND METHODS: Liver fibrosis was induced by intraperitoneal injection of Carbon tetrachloride (CCl4) in C57BL/6 mice for 6 weeks. From week 4 to week 6, the CCl4-injected mice were randomly divided into three groups, followed by oral administration of Sorafenib, XFZY and water for 3 weeks. Biochemical parameters, hydroxyproline (Hyp) content and histological changes of the liver were determined. The expressions of alpha smooth muscle actin (α-SMA), collagen I, CD31 and vascular endothelial grow factor (VEGF) were assessed by immunohistochemistry and western blot. The protein expressions of VEGFR-2, hypoxia inducing factor (HIF)-1α, asymmetric dimethylarginine (ADMA) and dimethylarginine hydrolase (DDAH) 1 were determined by western blot. The mRNA levels of α-SMA, VEGF and HIF-1α were measured by RT-PCR. RESULTS: Both Sorafenib and XFZY improved biochemical parameters of the liver fibrosis mice. A significant reduction in Hyp content was found in the XFZY-treated mice as well as the Sorafenib-treated mice. Changes in histopathology showed that Sorafenib and XFZY decreased inflammatory and fibrotic stages of the liver in fibrosis mice. Compared to CCl4 model group, Sorafenib and XFZY decreased α-SMA, collagen I, CD31, VEGF, VEGFR-2, HIF-1α and ADMA, and increased the expression of DDAH1. CONCLUSION: XFZY inhibits liver fibrosis not only through inhibiting collagen deposition but also through an antiangiogenic effect on the fibrotic liver. Moreover, the antiangiogenic mechanism of XFZY involves alleviating hypoxia and protecting liver sinusoidal endothelial cell function.
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Inibidores da Angiogênese/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Fitoterapia , Actinas/genética , Actinas/metabolismo , Amidoidrolases/metabolismo , Inibidores da Angiogênese/farmacologia , Animais , Tetracloreto de Carbono , Colágeno Tipo I/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos C57BL , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To investigate the effects of ancient Chinese medical formula Xiayuxue Decoction ([symbols; see text], XYXD) on activation of hepatic stellate cells (HSCs) and defenestration of sinusoidal endothelial cells (SECs) in CCl4-induced fibrotic liver of mice. METHODS: High performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCl4 exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 (CD31). Whole liver lysates were detected of α-smooth muscle actin (α-SMA) and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA, F-actin, DNA fragmentation through confocal microscopy, Western blot, terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan, respectively. RESULTS: Amygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% (P<0.01), as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% (P<0.05) respectively. In vitro, XYXD (12.5 µg/mL, 50 µg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent, demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% (P<0.05). Besides, XYXD induced the apoptosis of HSC-T6 cells by 20.0% (P<0.05) and 49.5% (P<0.01), evidenced by enhanced TUNEL positivity. Moreover, ultrastructural observation suggested XYXD inhibited defenestration of SECs, which was confirmed by 31.1% reduction of protein level of CD31 (P<0.05). CONCLUSIONS: XYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases.