淫羊藿素通过抗氧化损伤延缓CCl_4诱导的大鼠肝硬化进程  

Effect of recombinant adenovirus livin siRNA on proliferation and apoptosis of U251 cells

作　　者：钱海华[1] 刘鹏[2] 李晶[1] 陈磊[1] 曹璐[1] 张瑞秀[1] 殷正丰[1] 

机构地区：[1]第二军医大学东方肝胆外科医院分子肿瘤实验室,上海200438 [2]海军总医院肝胆外科,北京100048

出　　处：《第二军医大学学报》2011年第6期625-629,共5页Academic Journal of Second Military Medical University

摘　　要：目的探讨淫羊藿素延缓大鼠肝硬化进程的作用及可能机制。方法用不同浓度淫羊藿素处理经CCl4损伤的体外培养大鼠原代肝细胞,测定细胞培养液中ALT、AST和MDA浓度、细胞内SOD含量及凋亡细胞数量。建立CCl4诱导的大鼠肝硬化模型,用淫羊藿素处理后检测各组大鼠血清ALT、AST、ALB、GLB浓度,并观察大鼠肝组织病理学变化和胶原蛋白Ⅰ表达情况。结果 CCl4损伤可使原代大鼠肝细胞培养上清中ALT、AST活性和MDA含量以及细胞凋亡率升高,细胞内SOD活性降低。用淫羊藿素预处理后,其培养上清中ALT、AST活性和MDA含量以及细胞凋亡率均明显低于凋亡模型组和药物载体组,细胞内SOD活性则明显高于模型组和药物载体组,差异有统计学意义(P<0.05或0.01)。体内研究结果显示,与模型组比较,淫羊藿素处理可降低肝硬化模型大鼠血清ALT、AST水平,改善肝功能指标(P<0.05)并减少胶原蛋白Ⅰ沉积,减轻肝硬化程度。结论淫羊藿素可能通过抗氧化损伤延缓CCl4诱导的肝纤维化向肝硬化发展的进程。Objective To investigate the role of icaritin in delaying the progression of liver cirrhotic process in rats and the related mechanism. Methods For in vitro study, primary rat hepatocytes were obtained by perfusing the liver of male Wistar rats; the cultured cells were exposed to the fresh medium containing CCI4, and then treated with various concentrations of icaritin. The activities of alanine transaninase （ALT） and glutamic-oxaloacetic transaminase （AST） in culture medium were measured with an automatic biochemical analyzer. The intracellular contents of malondialdehyde （MDA） and superoxide dismutase （SOD） were determined by spectro-photometry; the apoptotic cells were detected by the TUNEL method. For in vivo study, CCL-indueed experimental rat hepatic fibrosis model was established and was treated with icaritin. Serum levels of ALT, AST, albumin（ALB）, and glohulin（GLB） were measured; the pathological changes and collagen Ⅰ expression in livers were observed by HE staining and immunohistochemistry, respectively. Results CC14 significantly increased the activities of ALT, AST, and the contents of MDA in culture media of hepatocytes, and significantly decreased the SOD activity. More apoptotic cells were observed in CC14 group than that in icaritin group. The ALT, AST activities in culture supernatant and the intracellular MDA contents in icaritin group were significantly lower than those in both model group and drug carrier group, while intraeellular SOD activity was much higher than that in other two groups （P〈0.05）. Icaritin also reduced the apoptotic ratios of hepatocytes induced by CC14 compared with model group （ P〈0.05 or 0. 01）. In the in vivo experiment, icaritin treatment significantly reduced serum levels of ALT and AST compared with model group （P〈0.05） and greatly improved CCl4-induced liver histopathological injuries and collagen I deposition in the liver tissues. Conclusion Icaritin treatment can attenuate CC14-induced cirrhosis in rats, at least in par

关 键 词：淫羊藿素 肝损伤 肝纤维化 细胞凋亡 

分 类 号：R575.2[医药卫生—消化系统]