目的研究糖尿病大鼠不同病程心肌纤维化及其相关病理的变化。方法①制造糖尿病大鼠心肌模型随机分组;②氯胺T法测定羟脯氨酸含量,代表心肌胶原总含量。心肌免疫组织化学染色测定心肌胶原蛋白(CollagenI、CollagenIII)和心肌型α肌动蛋白(α-actin)及转化生长因子β1平均积分光密度;③心肌病理改变的光镜和透射电镜观察。结果糖尿病病程6个月组心肌胶原总含量明显高于病程3个月以内组(P<0.01)。病程3个月之后CollagenI表达伴随TGF-β1的表达开始较健康鼠明显增加(P<0.01)。α-actin蛋白表达较健康鼠明显减少(P<0.01)。病程3个月后α-actin蛋白表达明显减少,有糖原沉积现象。结论CollagenI呈现持续性增加是糖尿病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。糖原沉积和心肌型actin表达减少是糖尿病心肌病病理基础。 Objective To study the changes of myocardial fibrosis and its related pathology in different course of diabetic rats. Methods ① The myocardium models of diabetic rats were randomly divided into groups; ② The content of hydroxyproline in chloramine T method was determined, which represented the total content of myocardial collagen. Myocardium immunohistochemical staining was used to determine the average integral optical density of Collagen III (Collagen III), α-actin and transforming growth factor-β1. ③ The pathological changes of myocardium were observed by light microscopy and transmission electron microscopy. Results The total content of myocardial collagen in the 6-month diabetic group was significantly higher than that in the 3-month group (P <0.01). After 3 months, the expression of CollagenI began to increase with the increase of TGF-β1 (P <0.01). α-actin protein expression was significantly reduced compared with healthy mice (P <0.01). After 3 months of course, the expression of α-actin protein was significantly reduced, with glycogen deposition. Conclusion The continuous increase of CollagenI is the main reason of myocardial fibrosis in diabetic rats. TGF-β1 is involved in the early course of myocardial fibrosis. Glycogen deposition and decreased expression of myocardial actin is the pathological basis of diabetic cardiomyopathy.