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

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.