糖尿病心肌病心肌细胞纤维化的病理改变

The pathologic changes of myocardial fibrosis in diabetes mellitus myocardiopathy

目的研究糖尿病(DM)大鼠不同病程心肌纤维化及其相关病理变化。方法选取18只DM心肌模型后大鼠随机分为DM大鼠1个月组(DM1组)、3个月组(DM3组)、6个月组(DM6组),每组6只。另选18只健康大鼠作为对照组。采用氯胺T法测定羟脯氨酸含量,为心肌胶原总含量。免疫组织化学染色测定心肌胶原蛋白Ⅰ、Ⅲ和心肌细胞心肌型α肌动蛋白(α-actin)及转化生长因子β1(TGF-β1)平均积分吸光度(A)。光镜和透射电镜下观察心肌病理变化。结果DM6组心肌胶原总含量明显高于DM1组和DM3组(P<0.01)。与对照组比较,DM3组心肌胶原蛋白Ⅰ表达伴随TGF-β1的表达开始明显增加(P<0.01)。心肌细胞心肌型α-actin表达较对照组明显减少(P<0.01)。各组大鼠心肌横切面可见粗大胶原纤维相互连接成网状,排列紊乱,分布不匀。α-actin表达明显减少,有糖原沉积现象。结论胶原蛋白Ⅰ呈现持续性增加是DM大鼠心肌纤维化的主要原因。TGF-β1参与了心肌纤维化发生的早期过程。糖原沉积和心肌细胞心肌型α-actin表达减少是DM心肌病的病理基础。

Objective To investigate pathologic changes of myocardial fibrosis at different stages of diabetes mellitus（DM） in rats. Methods Myocardium models of 18 DM rats were divided into 3 groups at random：DM rats one month（DM1） group,three months （DM3） group and six months （DM6） group. Eighteen healthy rats served as controls. The hydroxy proline contents were measured with the chloramine T method. The type-Ⅰ collagen,type-Ⅲ collagen,transforming growth factor beta1 （TGF-β1） and cardiac-type α-actin were determined by myocardial immunohistochemical stain. Myocardial pathologic changes were observed under light microscope and transmission electron microscope. Results The collagen content of DM6 group was significantly higher than that of DM1 and DM3 groups （ P 〈0.01）. Compared with the confrol group,expression of myocardial collagen I in DM3 group began to increase significantly with expression of TGF-β1 （P〈0.01）. Expression of α-actin in DM rats significantly decreased as compared with control group （P 〈0.01）. Cross section of myocardium of DM rat showed that the thick collagenous fibers connected with each other to form a network,they were arranged irregularly and distributed unevenly. The expression of α-actin decreased significantly and there was phenomenon of glycogen deposition. Conclusions Continuous incrcease in type-1 collagen is the main cause of myocardial fibrosis of DM rat. TGF-β1 participates in the early process of development of myocardial fibrosis. Decrease in expression of myocardial type α-actin and deposition of glycogen are the pathologic basis of DM myocardiopathy.