依那普利对肝组织bax和bcl-2基因表达的影响

Mechanism of preventive and therapeutic effects of enalapril on liver fibrosis in rats:the effect of enalapril on bax and bcl-2 genes

目的探讨血管紧张素转化酶抑制剂(ACEI)依那普利(Ena)对大鼠肝纤维化的防治作用及其部分机制,及对肝组织bax和bcl-2基因表达的影响。方法以四氯化碳(CCl_4)诱导形成大鼠肝实质损伤性肝纤维化模型。大鼠分为空白对照组、模型对照组、预防组及治疗组。除空白对照组外,其余各组大鼠均皮下注射40％CCl_4橄榄油混合液,每3日1次,共10周。预防组同时给予Ena灌胃。治疗组则在造模第5周给予Ena灌胃。对肝组织标本炎症及纤维化程度进行评价,并用RT-PCR技术观察Ena对肝组织bax和bcl-2基因表达的影响。结果Ena高剂量预防及高剂量治疗组肝组织炎症和纤维化程度较模型对照组显著减轻(P＜0．01)。Ena高剂量预防及高剂量治疗组肝组织bax基因表达显著弱于模型对照组(P＜0．01),bcl-2基因表达显著强于模型对照组(P＜0．01),bax/bcl-2基因表达比值和肝纤维化程度呈显著直线正相关(P＜0．01)。结论Ena能有效防治大鼠肝纤维化,抑制促凋亡基因bax的表达,促进抑凋亡基因bcl-2的表达,是其可能机制之一。bax/bcl-2基因表达比值与肝纤维化程度正相关。

Objective To investigate the effects of angiotensin-converting enzyme inhibitor, Enalapril, on extent of liver fibrosis in experimental fibrotic rats and possible mechanisms. Methods Liver fibrosis in rats was induced by CC14. Rats were assigned into control group, model group, prevention group and treatment group. Except rats in control group, all rats were given subcutaneous injection of 40% CCl4 once every 3 days for 10 weeks. Rats in prevention group were also given Enalapril via gastrogavage. And rats in treatment group were given Enalapril from the fifth week to the end of the study via gastrogavage. At the end of the tenth week, the extent of liver inflammation and fibrosis was evaluated. The effects of Enalapril on bax and bcl-2 genes expression of liver tissues were determined by RT-PCR techniques. Results Compared with model group, higher dose Enalapril in prevention and treatment groups could eonsiderablely attenuate the extent of liver inflammation and fibrosis （P 〈 0.01）. The expression intensity of bax gene of Enalapril in prevention group and treatment group with higher dose was decreased significantly as compared with model group （P 〈 0.01）. The expression intensity of bcl-2 gene of Enalapril in prevention and treatment groups with higher dose were increased significantly as compared with model group （P 〈 0.01）. A significant positive linear correlation was found between the expression of bax gene/bcl-2 gene and the extent of liver fibrosis （P 〈 0.01）. Conclusions Enalapril could effectively prevent and treat liver fibrosis through inhibiting the expression of the promoting apoptosis gene bax and restraining apoptosis gene bcl-2. There was a significant positive correlation of the expression of bax gene/bcl-2 gene with the extent of liver fibrosis.