青蒿琥酯对肝纤维化大鼠肝组织基质金属蛋白酶表达的影响  

Effects of artesunate on MMPs expression in hepatic fibrosis of rats

作　　者：刘文东[1] 李英娴[1] 娄婷婷[1] 高思楠[1] 方步武[1] 

机构地区：[1]天津医科大学药理学教研室,天津300070

出　　处：《天津医科大学学报》2013年第5期362-364,372,共4页Journal of Tianjin Medical University

基　　金：国家自然科学基金资助项目(30772856)

摘　　要：目的:研究青蒿琥酯对肝纤维化大鼠肝组织中基质金属蛋白酶(MMPs)及Ⅰ型胶原表达的影响,探讨青蒿琥酯对大鼠肝纤维化的治疗作用。方法:Wistar大鼠随机分为6组:正常组、模型对照组、青蒿琥酯低、中、高剂量组(3.2 mg/kg、9.6 mg/kg、28.8mg/kg)及马洛替酯阳性对照组(53.1 mg/kg),每组10只大鼠。牛血清白蛋白(BSA)免疫性大鼠肝纤维化模型制备成功后,各组按相应药物剂量分别开始治疗,正常组和模型组给予同体积蒸馏水,每日1次,连续2个月至实验结束。酶谱法测定肝组织MMP-2,MMP-9的表达;Western blotting检测肝组织Ⅰ型胶原与MMP-13的表达。结果:(1)肝组织Ⅰ型胶原的表达:与正常组比较,模型组大鼠肝组织Ⅰ型胶原含量增高(P<0.01);与模型组比较,各治疗组大鼠肝组织Ⅰ型胶原含量均降低(P<0.05)。(2)肝组织基质金属蛋白酶的表达:与正常组比较,模型组大鼠肝组织MMP-2、MMP-9表达增高(P<0.01);与模型组比较,各治疗组大鼠肝组织MMP-2、MMP-9表达均降低(P<0.01),MMP-13表达升高(P<0.01)。结论:青蒿琥酯可能通过降低肝组织MMP-2、MMP-9的表达,增加MMP-13的表达,从而发挥抗肝纤维化的作用。Objective： To investigate the effects of artesunate on expression of matrix metalloproteinases（MMPs） and type I collagen in ex- perimental hepatic fibrosis of rat. To study the action mechanism of artesunate for t^atment of immuno-injured hepatic fibrosis. Methods： Wistar rats were randomly divided into 6 groups： normal group, model group, group with low dose of artesunate （3.2 mg/kg）, group with mid- die dose of artesunate（9.6 mg/kg）, group with high dose of artesunate（28.8 mg/kg） and malotilate group（53.1 mg/kg）. Liver fibrosis models of rats were made by intravenous injection via the tail vein with bovine serum albumin （BSA） saline solution. Drugs were given to the colwe-- sponding therapeutic groups once a day for two months. Distilled water was given to the rats of normal and model groups according to the same method. Liver tissues were used for measuring the contents of collagen I and MMPs by the methods of gelatin zymography and Western blotting. Results： Expression of MMP-2, MMP-9 and collagen I were enhanced in model group （P〈0.01, P〈0.01, P〈0.05） and markedly weakened in therapeutic groups （P〈0.01, P〈0.01, P〈0.01）. Compared the model group, expression of MMP-13 was significantly enhanced （P〈0.01）. Conclusion： Anti-hepa6c fibrosis function of artesunate may be related to its inhibiting the MMP-2 and MMP-9 expressions and enhancing the MMP-13 expression.

关 键 词：青蒿琥酯 肝纤维化 基质金属蛋白酶 Ⅰ型胶原 大鼠 

分 类 号：R96[医药卫生—药理学] R575[医药卫生—药学]