贝那普利抑制糖尿病大鼠心肌间质纤维化的机制探讨

Experimental Study of Benazepril on Inhibiting Myocardial Interstitial Fibrosis of Diabetic Rats

目的研究血管紧张素转换酶抑制剂贝那普利(Benazepril)对糖尿病大鼠心肌间质纤维化过程的影响及保护机制。方法30只SD大鼠随机分为对照组10只,糖尿病组10只和贝那普利组10只。糖尿病组和贝那普利组采用链脲佐菌素(STZ,50mg/kg)腹腔内注射,建立糖尿病模型。贝那普利组大鼠用贝那普利(5mg/kg)治疗10周。用免疫组化法测Ⅰ、Ⅲ型胶原,转化生长因子(TGF-β1)、基质金属蛋白酶组织抑制因子(TIMP-1)、基质金属蛋白酶(MMP-1)蛋白的表达;RT-PCR法测TIMP-1、MMP-1 mRNA的表达。结果糖尿病组大鼠心脏指数、心室指数均显著高于正常对照组,心肌间质纤维化,胶原Ⅰ、胶原Ⅲ含量增加,TGF-β1、TIMP-1蛋白及TIMP-1 mRNA的表达增高,MMP-1蛋白及MMP-1 mRNA的表达减少。贝那普利治疗后,上述指标均有所改善。结论贝那普利可能通过对TGF-β1和基质金属蛋白酶的影响明显改善糖尿病心肌间质纤维化。

Object To investigate the effects of ACEI-benazepril on the contents of myocardial signals, and its protective effect on myocardium and probable mechanism in diabetic rats. Methods 30 male SD rats were randomly put into two groups, 10 as normal control group and the others as the diabetic group. The diabetes mod- els were set up with 50 mg/kg streptozotocin（STZ） intraperitoneal injection to the 20 SD rats and then benazepril （5 mg/kg） was used to treat diabetes rats for ten weeks. Immunohistochemistric method was used to measure expression levels of typeⅠ collagen, type Ⅲ collagen, transforming growth factor betal （TGF-β1） protein, matrix metalloproteinases （MMP）-1 and tissue inhibitors ofmetalloproteinases（T1MP）-1 protein. The mRNA of MMP-1 and TIMP- 1 mRNA were measured by RT-PCR.Results By the end ofexpriment, the cardian index and the ventricle index were significantly higher in the DM group than in the normal （P〈0.05）. The expression of type Ⅰ , type Ⅲ collagen, TGF-β1 protein, TIMP-1 protein and mRNA were also significantly higher than in the normal while the expression of MMP-1 protein and mRNA were significantly lower.All those indexes were greatly improved in the treated groups compared with the DM group. There was no significantl different between the two groups.Conclusion By decreasing the expression of AnglI, further influencing the expression of TGF-β1, MMp-1 and TIMP-1, and the benazepril could influence the myocardial intertitial fibrosis of diabetic rat.