脂质过氧化在二甲基亚硝胺大鼠肝纤维化形成过程中的作用  

Role of lipid peroxidation in liver fibrogenesis induced by dimethylnitrosamine in rats

作　　者：陈文慧[1] 刘平[1] 徐光福[1] 陆雄[1] 熊卫国[1] 李风华[1] 刘成海[1] 

机构地区：[1]上海中医药大学肝病研究所,上海市200032

出　　处：《世界华人消化杂志》2001年第6期645-648,共4页World Chinese Journal of Digestology

基　　金：上海市教育发展基金会上海市教委曙光计划;No.99SG44

摘　　要：目的探讨脂质过氧化损伤在二甲基亚硝胺诱导大鼠肝纤维化形成中的作用。方法二甲基亚硝胺腹腔注射4wk诱导大鼠肝纤维化模型,连续每周动态观察染毒4wk及染毒停止后4wk大鼠血清肝功能(ALT,AST,清蛋白、总胆红素)、肝组织羟脯氨酸(Hyp)含量、SOD、GSH与GSH-PX活性、MDA含量等变化,连续同步观察大鼠肝组织炎症坏死与胶原沉积等的变化。结果模型大鼠血清肝功能明显异常,ALT自2wk开始升高,4wk达高峰,以后维持较高水平;总胆红素自2wk出现异常;清蛋白含量自1wk开始下降,5wk时为最低,4wk时肝组织HE染色见汇管区肝细胞浸润及较广泛出血坏死,胶原染色显示有宽大纤维间隔形成,至8wk时仍较明显,肝组织Hyp含量2wk时轻微增加,4wk时达高峰。而后持续较高水平,2wk 3wk时,大鼠肝组织SOD与GSH-PX活性下降、GSH含量下降、MDA含量上升,并达到高峰,相关分析发现,肝脏Hyp含量与SOD活性明显负相关,而与MDA含量之间呈显著的正相关。结论脂质过氧化显著损伤出现在肝脏胶原沉积之前,两者之间明显相关,脂质过氧化损伤是二甲基亚硝胺诱导大鼠肝纤维化形成的重要机制。AIM To investigate the role of lipid peroxidation in the liver fibrogenesis induced by dimethylnitrosamine in rats. METHODS The liver fibrotic model was induced by i.p. dimethylnitrosamine (DMN) for 4 wk. While making model for 4 wk and an other 4 wk after stopping intoxication, the following indexes were observed consecutively each week: serum liver function including ALT, AST, albumin and total bilirubin, Hyp content of liver tissue, SOD, GSH and GSH-PX activities, MDA contents etc, Hepatic tissue inflammation and necrosis, collagen deposition in liver were observed at the same time. RESULTS The liver function was obviously abnormal in the model, ALT increased from the second week and got its highest one at the fourth week. The total bilirubin changed at the second week, while albumin content decreased at the first week and went down to the lowest at the fifth week. At the fourth week, there were inflammatory cell infiltration in the portal areas and widely bleeding and necrosis, and the wide fibrous septa were formed, which remained obvious at the eighth week, The hepatic Hyp level slightly increased at the second week, reached the peak at the fourth week and sustained high level later. At week 1 2, SOD and GSH-PX levels decreased significantly, GSH decreased but MDA content increased in hepatic tissue, and these changes reached their peaks at week 2-3. Hepatic Hyp content was negatively related to SOD activity, but positively to MDA content. CONCLUSION Lipid peroxidation occurred before collagen deposition in liver during DMN induced fibrogenesis, they were significantly correlated. The lipid peroxidation injury was one of the main mechanisms of liver fibrogenesis induced by DMN in rats.

关 键 词：肝纤维化 脂质过氧化 胶原 二甲基亚硝胺 

分 类 号：R575.2[医药卫生—消化系统]