依那普利对大鼠肝纤维化的预防和治疗作用

Preventive and therapeutic effects of enalapril on liver fibrosis in rats

目的:探讨血管紧张素转化酶抑制剂(ACEI)依那普利(Ena) 对四氯化碳(CCl4)诱导的大鼠实验性肝纤维化的预防和治疗作用. 方法:以CCl4诱导形成大鼠肝实质损伤性肝纤维化模型.大鼠分为对照组、模型组、预防组及治疗组.除对照组外, 其余各组大鼠均sc 400mL/L CCl4橄榄油混合液,每3d/次, 共10wk.预防组同时给予Ena灌胃.治疗组则在造模第5wk 给予Ena灌胃.实验结束后称量肝脾并收取肝组织.通过HE 及Masson三色染色对肝组织炎症及纤维化程度进行评价,通过透射电镜观察肝细胞超微结构. 结果:用药后,与对照组相比,模型组、Ena预防及治疗组体质量均显著下降(P<0.01).与模型组相比,Ena预防及治疗组大鼠肝脾指数均显著降低(P<0.01),Ena高剂量预防及高剂量治疗组均显著改善肝组织炎症和纤维化程度(P<0.01).通过电镜观察肝细胞,Ena高剂量预防及高剂量治疗组肝细胞损害较模型组明显减轻. 结论:依那普利对CCl4诱导的大鼠实验性肝纤维化有良好的预防和治疗作用.

AIM: To study the effects of angiotensin-converting enzyme inhibitor, enalapril, on the extent of liver fibrosis in experimental fibrotic rats induced by carbon tetrachloride (CCl4) METHODS: Liver fibrosis in rats was induced by CCI4. Rats were assigned into control group, model group, prevention groups and treatment groups. Except for rats in control group, all rats were given subcutaneous injection of 400 mL/L CCI4, once every 3 days for 10 weeks. Rats in prevention groups were also given enalapril via gastrogavage. But rats in treatment groups were given enalapril from the fifth week to the end via gastrogavage. At the end of tenth week, livers and spleens were measured and specimens of liver were stored. The extent of liver inflammation and fibrosis was evaluated with HE and Masson staining. We also observed the ultrastructures of hepatocytes under electron microscope. RESULTS: After using enalapril, the body weights of model group, enalapril prevention groups and enalapril treatment groups decreased significantly as compared with that of control group (P<0.01). Compared with model group, the liver and spleen indexes of enalapril prevention and treatment groups decreased significantly (P <0.01), enalapril prevention and treatment groups of higher dose considerablely attenuated the extent of liver inflammation and fibrosis (P<0.01). The extent of hepatotic injury in enalapril prevention and treatment groups of higher dose decreased significantly than that of model group under electron microscope. CONCLUSION: Enalapril has better preventive and therapeutic effects on experimental liver fibrosis in rats induced by CCl4.