链脲佐菌素致糠尿病大鼠心肌结缔组织生长因子及蛋白激酶C表达的实验研究

Experimental study on the expression of connective tissue growth factor and protein kinase C in myocardium of Diabetic Rats

目的:从基因和蛋白水平阐明结缔组织生长因子(CTGF)在糖尿病大鼠心肌病变形成过程中的表达及其与蛋白激酶C(PKC)、心肌纤维化的关系,探讨CTGF在糖尿病心肌病中的作用。方法:SD大鼠随机分为正常组(N组)、链脲佐菌素致糖尿病组(D组),在此基础上又分为四周组(N4、D4)和八周组(N8、D8),免疫组化检测心肌纤维连接蛋白(FN)、CTGF、PKC的表达;RT-PCR检测心肌组织中CTGFmRNA水平。结果:与N组相比,糖尿病大鼠心肌CTGF蛋白的表达逐渐增高,与FN、PKC蛋白表达进行性增高相平行;CTGFmRNA表达逐渐增高。结论:在糖尿病早期,心肌中PKC表达随着病程的延长而增多,通过CTGF表达的增多,引起FN表达的改变,从而促进心肌纤维化。

Objective. To evaluate the role of CTGF in the pathogenesis of diabetic cardiomyopathy and the relation of PKC,CTGF and interstitial fibrosis, and to provide the evidence of the treatment in DCM state. Methods. Sprague-Dawley（SD） rats were divided into 4 groups randomly： the normal control group（N4,N8） and the diabetic group（D4,D8）. Diabetes was induced by Streptozotocin（STZ） intraperito- neal injection in SD rats of diabetic group. The protein expression of CTGF, PKC and FN were compared between the two groups of various duration by immunohistochemistry method. The RT-PCR was em- ployed to detect the gene expression of CTGF. Results= Notable upregradulation of CTGF protein coincide with an apparent increase of PKC and FN expression in diabetic myocardium. These alterations were en- hanced gradually along with longer diabetic duration;The expression of CTGF mRNA was enhanced grad-ually along with longer diabetic duration. Conclusions. In diabetic myocardium, PKC is enhanced gradually along with longer diabetic duration. It promotes the expression of FN by CTGF, and causes myocardium fibrosis.