不同功效古典方剂对肝硬化大鼠肝组织氧化应激反应的影响

Effects of 5 Classical Recipes on Anti-oxidative Stress in Rat Liver with Cirrhosis

目的比较5首不同功效古典方剂逆转二甲基亚硝胺(DMN)诱导的大鼠肝硬化的抗肝组织氧化应激效应。方法4周内给大鼠腹腔注射DMN 12次制备肝硬化模型,成模后停止染毒,随机分为模型对照组、一贯煎组、黄芪汤组、茵陈蒿汤组、下瘀血汤组及小柴胡汤组,分别以生理盐水或相应药物灌胃给药2周;检测各组大鼠肝组织总超氧化物歧化酶(T-SOD)、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽-S转移酶(GST)活性及丙二醛(MDA)含量及血清肝功能、肝组织羟脯氨酸(Hyp)含量的变化。结果与正常组比较,模型大鼠肝组织GST活性及MDA含量显著升高,分别于造模2周末(肝纤维化形成期)、4周末(肝硬化形成)达到高峰,而T-SOD及GSH-Px活性显著降低;与6周模型组比较,黄芪汤组和茵陈蒿汤组大鼠肝硬化明显减轻,肝组织MDA含量及GST活性显著下降,T-SOD活性显著升高。结论氧化应激是DMN诱导大鼠肝硬化形成的重要病理环节,抗氧化应激效应是茵陈蒿汤和黄芪汤逆转大鼠肝硬化的主要机制之一。茵陈蒿汤的祛邪作用重在清除脂质过氧化物等病理因子,黄芪汤的扶正效应重在提高机体内在的抗氧化能力。

Objective To compare the anti-oxidative stress effects of 5 classical traditional Chinese herbal recipes in rats with dimethylnitrosamine （DMN）-induced cirrhosis. Methods DMN was injected intraperitoneally three consecutive days a week to male Wistar rats for 4 weeks to develop cirrhosis model, and the model cirrhotic rats were randomly grouped and administered with 5 traditional Chinese classic recipes, i.e. Yiguanjian; Huangqi Decoction; Yinchenhao Decoction; Xiayuxue Decoction and Xiaochaihu Decoction, by gastrogavage, respectively, for 2 weeks. Changes in activity of total superoxide dismutase （T-SOD）, glutathione peroxidase （GSH-Px）, glutathione-S-transferase （GST） and malondialdehyde （MDA） content in liver tissue, and serum parameters of liver function were determined. Results GST activity and MDA content increased significantly in model rats, peaked at week 2 （ liver fibrosis formation period） and week 4 （ cirrhosis formation period）, respectively, while activity of T-SOD and GSH-Px decreased markedly. As compared with the model control group at week 6, the degree of cirrhosis was evidently milder with lower level of MDA and GST and higher T-SOD activity in rats treated by Huangqi Decoction and Yinchenhao Decoction. Conclusion Anti-oxidative stress action should be one important mechanism for Yinchenhao Decoction and Huangqi Decoction in reversing liver cirrhosis of rats. The action of Yinchenhao Decoction focuses on eliminating hepatic lipid peroxide and that of Huangqi Decoction emphasizes for enhancing anti-oxidation ability of the organism.