咪达普利与福辛普利对糖尿病大鼠心肌间质重构的影响

Comparison of Imidapril and Fosinopril in Improving Myocardial Interstitial Remodeling of Diabetic Rats

目的:用咪达普利(达爽)及福辛普利(蒙诺)两种血管紧张素转换酶抑制剂(ACEI)对实验性糖尿病大鼠进行早期干预,观察两药对糖尿病大鼠心肌间质重构的影响,了解两药对糖尿病大鼠心脏的保护作用有无区别。方法:以链脲佐菌素对30只SD大鼠进行腹腔注射,建立实验性糖尿病大鼠模型3组,包括咪达普利干预组,福辛普利干预组,糖尿病对照组,另外取10只SD大鼠作为正常对照组。用免疫组化法检测Ⅰ和Ⅲ型胶原含量;免疫组化法检测转化生长因子β1(TGF-β1)、基质金属蛋白酶1(MMP-1)、基质金属蛋白酶组织抑制剂1(TIMP-1)蛋白含量的表达,逆转录-聚合酶链反应(RT-PCR)检测MMP-1和TIMP-1的mRNA表达。结果:糖尿病对照组心脏指数及心室指数显著大于正常对照组,反映间质重构的指标Ⅰ和Ⅲ型胶原、TGF-β1、TIMP-1蛋白及TIMP-1 mRNA的表达均增加,而MMP-1蛋白及mRNA的表达减少。咪达普利干预组和福辛普利干预组的上述各种异常指标均有所改善,但两组的改善程度无显著差异。结论:含羧基的咪达普利与含磷酰基的福辛普利作为ACEI类药物,均可通过对TGF-β1和基质金属蛋白酶的影响而改善实验性糖尿病大鼠心肌间质的重构,两者对心脏间质的保护作用无明显差异。

Objective： To investigate whether imidapril and fosinopril have different effects in improving myocardial remolding in diabetic rats.Methods： Male SD rats were randomly assigned to one normal control group and three streptozotocin（STZ） induced diabetic groups as diabetic control group,imidapril treated group and fosinopril treated group.Immunohistochemistry was used to measure the expression levels of type Ⅰ collagen,type Ⅲ collagen,transforming growth factor beta1（TGF-β1） protein,matrix metalloproteinases（MMP）-1 and tissue inhibitors of metalloproteinases（TIMP）-1 protein.The mRNA of MMP-1 and TIMP-1 mRNA were measured by RT-PCR.Results： By the end of the experiment,the cardiac index and the ventricle index were significantly higher in diabetic group than in normal（P〈0.05）.The expression of typeⅠ,typeⅡcollagen,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 these changes were less in the two treatment groups when compared with those in diabetic conrtrol group.And there was no significant difference between the two treatment groups.Conclusion： The two ACEIs,imidapril and fosinopril have the same effect in improving the myocardial interstitial reconstruction by influencing the expression of TGF-β1 and MMPs in the experimental diabetic rats.There was no significant difference between them in improving the reconstruction of myocardial interstitial.