【摘要】 目的探讨血管紧张素转换酶抑制剂（ACEI）依那普利是否对 CCl₄引起的大鼠肝纤维化有阻滞作用。方法采用 CCl₄损伤引起的肝硬化门脉高压大鼠模型,随机分为正常对照组、肝硬化模型组、依那普利治疗组。治疗组在用 CCl₄造模的同时用依那普利灌胃,1次/d,直到造模结束,取部分肝组织用甲醛固定后行苏木素-伊红（HE）染色和 Masson 染色并进行肝硬化分级;然后根据染色结果制作组织芯片并行免疫组织化学染色,检测Ⅰ、Ⅲ型胶原的蛋白表达并进行半定量分析。取部分肝组织用逆转录（RT-PCR）法检测Ⅰ、Ⅲ型胶原的 mRNA 表达并进行半定量分析。结果肝硬化分级和 Masson 染色胶原半定量结果证实肝硬化模型组、依那普利治疗组大鼠肝纤维化程度明显加重,与对照组比较差异有统计学意义（P<0.01）;而依那普利治疗组的肝纤维化程度较模型组明显减轻,差异有统计学意义（P<0.05）。Ⅰ、Ⅲ型胶原免疫组织化学蛋白表达及 mRNA 表达结果证实肝硬化模型组与对照组、依那普利治疗组比较明显上调（P<0.05）。结论 ACEI 可以有效地下调 CCl₄引起的肝纤维化大鼠的Ⅰ、Ⅲ型胶原的蛋白表达和 mRNA 表达,进而抑制大鼠肝纤维化的发展。更多还原

【Abstract】 Objective To investigate whether angiotensin-converting enzyme inhibitor(ACEI) can arrest or reverse the progression of carbon tetrachloride(CC14)-induced cirrhosis in rats.Methods Hepatic cirrhosis with portal hypertension was induced in S-D rats by 50% CC14 treatment(3 ml/kg,in- tragastric administration,once/5 days).These rats were randomly assigned to one of the following groups: normal control,model and ACEI treatment groups.Rats in ACEI treatment group were then treated respec- tively with Enalapril(intragastric administration,10 mg/kg,once every day),concurrently with CC14 for 75 days.The rats were executed after anaesthesia.Formalin-fixed sections of the liver were stained with H&E and Masson.Inflammation and fibrosis were assessed histologically.According to the H&E staining results,tissue array was made,and collagen Ⅰ and collagen Ⅲ were measured by immunohistoehemistry. Relative mRNA expression of collagen Ⅰ and collagen Ⅲ was detected by semiquantitative reverse tran- seriptase-polymerase chain reaction(RT-PCR).Results The result of liver fibrosis stages and collagen semi-quantity of Masson stain showed that in the model group and ACEI treatment group the severity of he- patic cirrhosis was significantly more than that in normal group(P<0.01).In ACEI treatment group,he- patic were significantly reduced stages of fibrosis and collagen semiquantitative of Masson stain than the model group.The expression of protein and mRNA of collagen Ⅰ and collagen Ⅲ 2were significantly up-regu- lation in the model group than in other groups(P<0.05).Conclusion Enalapril(ACEI)can cause ef- fectively down-regulation expression of protein and mRNA of collagen Ⅰ and collagen Ⅲ in hepatic fibrosis rats by CC14 treatment.更多还原