谷胱甘肽复方注射液对免疫性肝纤维化大鼠肝组织MMP-13及TIMP-1表达的影响  

Effect of compound glutathione inosine injection on the expression of MMP-13 and TIMP-1 in rats with immunological hepatic fibrosis

作　　者：李伟[1] 梁跃东[1] 曾经章[1] 程明亮[1] 吴君[1] 

机构地区：[1]贵阳医学院感染病学教研室,贵阳550004

出　　处：《中国新药杂志》2011年第8期730-735,共6页Chinese Journal of New Drugs

摘　　要：目的:研究谷胱甘肽复方注射液(CGII)对猪血清所致免疫性肝纤维化大鼠肝组织中基质金属蛋白酶-13(MMP-13)以及组织抑制剂-1(TIMP-1)mRNA和蛋白表达的影响。方法:猪血清腹腔注射8周,复制大鼠免疫性肝纤维化模型。将雄性Wistar大鼠随机分为正常组(N组)、模型组(M组)、还原型谷胱甘肽(GSH)组、CGII高(CH,10.8 mg·kg-1)、中(CM,5.4 mg·kg-1)、低(CL,2.7 mg·kg-1)剂量组,第6周末取大鼠肝组织行病理切片,苏木素-伊红(HE)染色,观察病理学改变;用实时荧光定量PCR和Western Blot检测大鼠肝组织中MMP-13以及TIMP-1 mRNA和蛋白的表达。结果:病理结果显示,与模型组相比,CH,CM和CL各组大鼠肝纤维化程度均有明显改善,大鼠肝组织内TIMP-1 mRNA及蛋白水平显著降低,MMP-13 mR-NA和蛋白表达水平明显升高。结论:CGII可明显减轻免疫性大鼠肝纤维化程度,其机制可能与下调TIMP-1 mRNA及蛋白水平,上调MMP-13 mRNA及蛋白水平,改善肝纤维化中MMP-13/TIMP-1的不平衡表达有关。Objective：To investigate the effect of compound glutathione inosine injection（CGII） on the expression of the matrix metalloproteinase-13（MMP-13） and the tissue inhibitor of metalloproteinase-1（TIMP-1） in rats with immunological hepatic fibrosis induced by porcine serum.Methods： Immunological liver fibrosis was induced by intraperitoneal injection of porcine serum for 8 weeks in male Wistar rats.Rats were randomly divided into 6 groups,and treated with 3 doses of CGII and glutathione（GSH,positive control）.At the end of the 6th week,hepatic histological changes were observed and scored under optical microscope after HE staining.The mRNA and proteins expressions of MMP-13 and TIMP-1 were detected by real-time RT-PCR and Western blotting.Results： Compared with liver fibrosis control,pathological lesion of liver fibrosis was obviously improved in rats treated by 3 doses of CGII.The mRNA and protein levels of TIMP-1 were significantly reduced but those of MMP-13 were obviously increased in rats treated by 3 doses of CGII as compared with liver fibrosis control.Conclusion： The development of hepatic fibrosis induced by porcine serum in rats is inhibited by CGII.The underlying mechanism might be related with decreasing the expression of TIMP-1 and increasing that of MMP-13.

关 键 词：肝纤维化 谷胱甘肽复方注射液 基质金属蛋白酶-13 基质金属蛋白酶组织抑制剂-1 

分 类 号：R965.1[医药卫生—药理学] R975.5[医药卫生—药学]