结缔组织生长因子在糖尿病大鼠心肌的表达及意义

Expression of Connective Tissue Growth Factor in the Myocardium of Diabetic Rats

目的观察结缔组织生长因子(CTGF)在糖尿病大鼠心肌中的表达,探讨CTGF在糖尿病心肌病发病机制中的作用。方法SD大鼠60只,均分为对照组和糖尿病组。链脲佐菌素(STZ)一次性腹腔注射建立糖尿病模型。在病程4,8,12周分别从2组中随机选择6只,称质量并计算心体比(H/B)和左室质量指数(LVMI)。电镜观察12周2组心肌超微结构,光镜观察2组冠状动脉病变。RTPCR方法比较不同病程各组心肌CTGF、纤维连接蛋白(FN)、Ⅲ型胶原(ColⅢ)、转化生长因子β1(TGFβ1)的表达。结果STZ诱导糖尿病组在病程12周心肌超微结构病变显著,冠状动脉未见病变,糖尿病心肌病已形成。在病程4,8,12周,糖尿病组H/B、LVMI逐渐增加,心肌CTGFmRNA表达显著上调(P<0.01),并随着病程延长呈逐渐增高趋势,与FN、ColⅢ表达进行性增高相平行。TGFβ1在糖尿病心肌中mRNA表达增高,但12周时已呈下降趋势。CTGF与TGFβ1mRNA表达呈正相关(r=0.792,P<0.01)。CTGF与FN、ColⅢmRNA表达呈明显正相关(r=0.923,0.879,均P<0.01),其相关性比TGFβ1显著。结论糖尿病大鼠心肌CTGF表达上调与细胞外基质的积聚密切相关,在糖尿病心肌病形成过程中,CTGF可能起较直接、持久的作用。

Objective To investigate the expression of connective tissue growth factor（CTGF） in the myocardium of diabetic rats and to evaluate the role of CTGF in the pathogenesis of diabetic cardiomyopathy. Methods Sixty SD rats were randomized into two groups, the normal control group and diabetic group. Diabetes was induced by streptozotocin（STZ） intraperitoneal injection. Six rats were selected at random from the two groups respectively at 4, 8, 12 weeks. The weights of body, whole heart and left ventricle were measured to calculate the ratio of heart weight to body weight（H/B） and the left ventricle mass index（LVMI）. The myocardial ultrastructure of the two groups at 12 weeks duration were obserbed by electron microscope, the coronary artery orifices were also observed by light microscope. The mRNA expression of CTGF, transforming growth factor β1 （TGF-β1）, fibronectin（FN）, collagen type Ⅲ （Col Ⅲ） were compared between the two groups of various duration by RT-PCR. Results In 12 weeks, STZ-induced diabetic SD rats showed conspicuous myocardial lesions. No abnormality was found along the coronary artery orifices. These results indicated the formation of diabetic cardiomyopathy. H/B and LVMI were increased in the diabetic group, which were aggravated with the course of diabetes. Notable upregradulation of CTGF mRNA coincided with an apparent increase of FN, Col Ⅲ expression in diabetic myocardium（P〈0.01 respectively）. These alterations were enhanced gradually along with diabetic duration. TGF-β1 mRNA expression was increased in the diabetic myocardium. But it appeared an downtrend in 12 weeks of diabetes. The expression of CTGF was positively correlative with that of TGF-β1 （r=0. 792 , P〈0. 01）. CTGF had a significant positive correlation with FN and Col Ⅲ（r=0. 923,0.879,P〈0. 01 respectively）, which was more obvious than that of TGF- β1. Conclusion Upregulation of CTGF is stongly correlated with the concomitant accumulation of extracellular matrix（ECM） component in the myocardium of diabetic rats. CTGF has more direct and persistent effect on the formation of diabetic cardiomyopathy.