芍芪多苷对肝纤维化大鼠肝脏星状细胞基质金属蛋白酶13及组织金属蛋白酶抑制因子1表达的影响  

Effects of Shaoqiduogan on MMP-13,TIMP-1 expression in liver and hepatic stellate cells of hepatic fibrosis rats

作　　者：孙妩弋[1] 桂双英[1] 吴丽[1] 王华[1] 魏伟[1] 

机构地区：[1]安徽医科大学临床药理研究所抗炎免疫药理学省部共建教育部重点实验室抗炎免疫药物安徽省工程技术研究中心,安徽合肥230032

出　　处：《中国中药杂志》2010年第11期1447-1451,共5页China Journal of Chinese Materia Medica

基　　金：国家高技术研究发展计划(863)项目(2002AA2Z3235);安徽省自然科学基金项目(090413108);安徽医科大学博士科研经费资助项目(XJ200804)

摘　　要：目的:研究芍芪多苷(SQDG)对四氯化碳(CCl4)诱导的肝纤维化大鼠肝组织和转化生长因子β1(TGF-β1)刺激的肝星状细胞(HSC)基质金属蛋白酶13(MMP-13)、组织金属蛋白酶抑制因子1(TIMP-1)表达的影响,探讨SQDG抗肝纤维化作用的可能机制。方法:CCl4皮下注射建立大鼠肝纤维化模型,设立正常对照组、模型组、SQDG给药组(42.5,85,170 mg.kg-1)。放免法检测血清中I型胶原(C-I)水平;Masson染色对肝脏组织作病理检查;免疫组化法检测肝组织MMP-13,TIMP-1的表达。采用Western blot探讨SQDG体外对TGF-β1刺激的HSC MMP-13,TIMP-1及C-I表达的影响。结果:SQDG可显著降低纤维化大鼠血清中C-I含量;病理组织学检查发现,SQDG可降低化学性肝纤维化大鼠的纤维化程度,与模型组相比,纤维沉积、肝小叶的破坏等均有所减轻。免疫组化结果显示,SQDG(85,170 mg.kg-1)可显著升高肝纤维化大鼠肝脏局部MMP-13水平,降低TIMP-1水平。进一步研究发现,SQDG体外可明显抑制TGF-β1刺激的HSC-T6 TIMP-1表达,促进MMP-13的表达,同时降低C-I的表达水平。结论:SQDG可能通过调节肝纤维化大鼠肝组织MMP-13和TIMP-1的异常表达,促进HSCMMP-13的表达,抑制TIMP-1的表达,促进胶原降解而发挥抗肝纤维化的作用。Objective：To investigate the effects of Shaoqiduogan（SQDG） on the expression of matrix metalloproteinase 13（MMP-13） and tissue inhibitor of metalloproteinase 1（TIMP-1） in carbon tetrachloride（CCl4） induced hepatic fibrosis rats and transforming growth factor β1（TGF-β1） irritated hepatic stellate cells（HSC）,and to explore its possible mechanisms.Method：The model of chemical hepatic fibrosis induced by CCl4 was prepared.The rats were randomly divided into 5 groups,including normal control group,liver fibrosis model group and SQDG（42.5,85,170 mg·kg-1） treated groups.The level of collagen type I（C-I） in serum was determined by radioimmunoassay.Masson stain was used to examine the histopathological change.MMP-13 and TIMP-1 expression in liver tissues were assayed by immunohistochemistry.In vitro,effects of SQDG on the expression of MMP-13,TIMP-1 and C-I in HSC-T6 stimulated by TGF-β were measured by Western-blot.Result：The results showed that SQDG significantly decreased the elevated level of C-I in serum of hepatic fibrosis rats induced by CCl4.Pathological examination showed that SQDG could remarkably alleviate the degree of liver fibrogenesis and formation of pseudolobulus.The results of immunohistochemistry demonstrated that SQDG significantly increased MMP-13 expression and decreased TIMP-1 expression in liver tissues.Furthermore,SQDG（20-160 mg·L-1） could facilitate MMP-13 expression,inhibit TIMP-1 expression and significantly inhibit the C-I production of HSC stimulated with TGF-β1 in vitro.Conclusion：The anti-fibrotic effects of SQDG may be associated with its action of promoting collagen degradation via controlling the levels of MMP-13 and TIMP-1 in liver.

关 键 词：芍芪多苷 肝纤维化 肝星状细胞 转化生长因子-Β1 

分 类 号：R285.5[医药卫生—中药学]