阻断肾素-血管紧张素-醛固酮系统不同环节对大鼠肝纤维化的影响

摘要

目的 探讨阻断肾素-血管紧张素-醛固酮系统(RAAS)不同环节对大鼠实验性肝纤维化的影响.方法 6周龄SD大鼠50只随机均分为空白对照(BC)组、模型对照(MC)组和A、B、C三个药物处理组.BC组腹壁皮下注射橄榄油；其余4组注射40％ CC14制备大鼠肝纤维化模型.次日,A组胃内灌注卡托普利60 mg/kg,B组胃内灌注氯沙坦10mg/kg,C组胃内灌注螺内酯100 mg/kg,1次/d;第8周处死,取材,HE染色和Masson染色观察肝组织病理变化,免疫组化、RT-PCR 及Western blot法检测肝组织转化生长因子β1(TGF-β1)表达.结果 A、B、C组肝纤维化程度均明显较MC组减轻(P＜0.05).MC组TGF-β1表达明显高于BC组(P＜0.05)和A、B、C组(P＜0.05),但A、B、C组三组间无明显差异.结论 阻断RAAS不同环节均可抑制肝纤维化形成,其作用可能与其降低TGF-β1表达有关.%Objective To investigate the effect of blocking renin-angiptensin-aldosterone system (RAAS) at different levels on hepatic fibrosis of rats. Methods Fifty SD rats aged 6 weeks were equally randomized into five groups. Ten rats were injected subcutaneously olive oil as blank controls (group BC). The hepatic fibrosis was induced in the rest rats with 40% CCl4 , which in group A was given captopril 60 mg/kg,in group B losartan 10 mg/kg,in group C spironolactone 100 mg/kg,and in model control group(MC) normal saline on the next day. The drugs were given by gastric gavage daily for 8 weeks. The rats were sacrificed on the 8th week. Hepatic fibrosis was evaluated by HE and Masson staining and the expression of transforming growth factor β1 (TGF-β1) in the liver was detected by immunohistochemistry, RT-PCR and Western blot. Results The severity of hepatic fibrosis was less in groups of A,B and C than that in group MC(P<0. 05). The expression of TGF-β1 in hepatic tissues was higher in group MC than that in the other 4 groups(P<0. 05), which was not significantly different among groups of A, B and C. Conclusion Blocking RAAS at different sites could suppress the development of hepatic fibrosis in rats, which may be related to an inhibition of TGF-β1 expression in hepatic tissues.