丹酚酸A对四氯化碳诱导的大鼠肝纤维化的防治作用及机制研究

Molecular mechanism of salvianolic acid A prevention against hepatic fibrosis induced by CCl_4 in rats

目的探讨丹参水溶性成分丹酚酸A对四氯化碳(CCl4)诱导的大鼠肝纤维化的防治作用及机制研究。方法将36只SD大鼠随机分为正常对照组(对照组)、肝纤维化组(模型组)和丹酚酸A给药组(给药组)。通过50%CCl4花生油溶液(1 m L·kg-1)灌胃诱导建立肝纤维化模型。给药组同时每日1次腹腔注射丹酚酸A 10 mg·kg-1。建模与给药期间观察大鼠基本生活状况,6周后处死大鼠,观察大鼠肝脏大体形态;用HE染色法进行肝脏病理学观察;全自动生化分析仪检测血清谷丙转氨酶(ALT)及谷草转氨酶(AST)的水平;放射免疫法测定血清透明质酸(HA)、Ⅳ型胶原(CⅣ)、层黏蛋白(LN)和Ⅲ型前胶原肽(PⅢP)的含量;Western blot检测肝脏组织中Bcl-2和Bax蛋白的表达。结果与模型组相比,丹酚酸A给药组能够显著降低大鼠血清ALT和AST的水平,明显降低大鼠血清肝纤维化指标,并改善大鼠肝脏病理组织学结构(P<0.05)。与模型组相比,丹酚酸A给药组能够促进肝脏组织中Bcl-2蛋白的表达,抑制Bax蛋白表达(P<0.05)。结论丹酚酸A可能是通过调节大鼠肝脏Bcl-2和Bax蛋白的表达来发挥其抗肝纤维化的作用。

Objective To determine the protective effect of salvianolic acid A（SA-A） on CCl4-induced hepatic fibrosis. Methods Thirty-six SD rats were randomly divided into a control group, a model group, and an SA-A group. Apart from the control group, rats in the other 2 groups were administered 50% CCl4（1 mL·kg^- 1） to induce hepatic fibrosis. Rats in the SA-A group were intraperitonealy injected SA-A 10 mg·kg^- 1 once every day besides CCl4. The basic living condition of the rats was observed for 6 weeks. After 6 weeks, macroscopic features of the liver were measured. Liver fibrosis of the rats was evaluated by HE staining. Activities of serum ALT and AST were checked with automated biochemistry analyzer. The serum levels of HA, C Ⅳ, LN and P Ⅲ P were detected by radioimmu-noassay. The expression of Bcl-2 and Bax was detected by Western blot. Results Compared with the model group, the pathologic manifestations improved and the activities of serum ALT, AST, HA, C Ⅳ, LN and P Ⅲ P reduced（P〈0.05） in the SA-A group. The expression of Bcl-2 protein was up-regulated and the expression of Bax protein was down-regulated in the SA-A group in the liver tissue. Conclusion SA-A can possibly prevent the progression of liver fibrosis by regulating the expression of Bcl-2 and Bax protein.