不同治则中药复方对胆汁淤积性肝纤维化大鼠PAI-1影响的研究

Effect of chinese medicine Complex prescriptions of different cure laws on PAI-1 mRNA of cholestasis-induced liver fibrosis rat

目的:观察补益肝肾、活血化瘀方剂二至丸、失笑散及其组合对胆汁淤积性肝纤维化大鼠肝组织PAI-1mRNA的影响。方法:采用胆管结扎复制胆汁淤积性肝纤维化模型。术后1周,造模组随机分模型组、优思弗、二至丸、失笑散及合方组;各药物干预组分别给予相应药物灌胃,模型组和假手术组给予等量生理盐水灌胃,至4周末处死全部动物取材。观察内容包括一般情况、肝功能(ALT、AST、ALP、TBil)、肝组织病理、PAI-1mRNA表达。结果:与假手术组比较,模型组大鼠ALT、AST、ALP、TBil、纤维化程度均显著升高;与模型组比较,3个复方均能降低胆汁淤积性肝纤维化大鼠血清ALP、ALT、AST水平(P<0.01),失笑散及合方能降低TBil(P<0.01);合方改善ALP、ALT优于两个单方。3个复方均能不同程度地减轻模型大鼠肝纤维化程度(P<0.01),合方优于两个单方。优思弗能降低ALT、AST水平,但对肝脏纤维化无明显改善作用。与模型组比较,失笑散组、二至丸组及合方组PAI-1mRNA表达显著降低(P<0.01),3个中药复方组之间比较,合方组最低,二至丸组次之,再次为失笑散组。结论:补益肝肾和活血化瘀中药复方二至丸、失笑散及其组合均不同程度地干预胆汁淤积性肝纤维化形成的作用,合方作用优于两个单方,其机制可能与调控PAI-1mRNA表达有关;不同治则的中药复方对PAI-1mRNA调控的强度不同。

Objective： To study the effects of the Chinese medicine complex prescriptions （Erzhiwas, Shixiaosan and Erzhiwan compound with Shixiaosan （ECS） on cholestasis-induced liver fibrosis rat＇s PAI-lmRNA. Methods： Using bile duct ligation method to make the model of cholestasis-induced liver fibrosis. One week after the operation, the rats were randomly divided into five group （model group, UDCA group, Erzhiwan group, Shixiaosan group and ECS group）. Each medicine intervention group was given corresponding medicine by intragastric administration. Sham ligation and model group were given sodium chloride with equal dosage. At the end of 4th week, all of the rats were sacrificed and sampled. General state of health, hepatic function （ALT, AST, ALP, TBil） and pathological histology of hepatic tissue were recorded and measured. Results： Comparing with the rats in sham ligation and model group, the level of ALT, AST, ALP, TBil and the degree of liver fibrosis of the rats in model group were advanced significantly. Comparing with model group, Three Chinese medicine complex prescriptions could decrease serum level of ALP, ALT and AST （P〈0. 01）. Shixiaosan and ECS could decrease serum level of TBil （P〈0.01）. ECS was better than simple recipe in ALP and ALT. All of three complex prescriptions could release liver fibrosis at some extent （P〈0.01）, but ECS was better than simple recipe. UDCA could decrease serum level of ALT and AST, but had no effect on liver fibrosis. Compared to model group, PAI-lmRNA expression significantly decreased in above three Chinese medicine complex prescription group （P〈0.01）, and ECS group was the lowest, Erzhiwan group was the middle, and Shixiaosan group was the highest. Conclusion.. Chinese mdeicine complex prescriptions （Erzhiwan, Shixiaosan and ECS） which have the function of tonify- ing liver and kidney and promoting blood circulation and removing blood stasis can inhibit the cholestasis-induced liver fi-brosis, and ECS was better than simple recipe. The mechanism was probably to regulate PAI-lmRNA expression. This study suggested that different Chinese medicine complex prescriptions possessed different regulatory intensity on PA1- lmRNA expression.