运动抑制转化生长因子β1/smad信号通路对糖尿病大鼠心肌纤维化影响的研究

Exercise prevents diabetic myocardial fibrosis by inhibiting TGF-beta1/smad signaling

目的观察运动对T2DM大鼠模型心肌纤维化的改善作用,探讨TGF-β1/smad信号通路的作用。方法腹腔注射STZ和高脂饮食建立T2DM大鼠模型,分为正常对照组(NC)、T2DM组和T2DM运动组(T2DME)。NC组和T2DM组安静饲养8周,T2DME组进行8周的跑台训练。运动结束后测体重、血糖。天狼星红染色观察心肌组织胶原蛋白水平,通过计算胶原容积分数(CVF)得出心肌纤维化程度。免疫荧光染色观察Ⅰ、Ⅲ型胶原蛋白的含量。Western blot测定心肌TGF-β1、smad2、p-smad2、smad3和p-smad3的含量。结果与NC组比较,T2DM组体重降低[(528±71)vs(362±33)g,P<0.05],血糖升高[(6.4±3.8)vs(26.0±7.5)mmol/L,P<0.01],心肌CVF升高[(2.2±0.31)%vs(5.8±0.45)%,P<0.01],心肌Ⅰ、Ⅲ型胶原蛋白、TGF-β1、p-smad2和p-smad3蛋白表达升高(P<0.05或P<0.01)。与T2DM组比较,T2DME组血糖降低[(26.0±7.5)vs(21.0±6.8)mmol/L,P<0.05],心肌CVF降低[(5.80±0.40)%vs(3.60±0.33)%,P<0.05],心肌Ⅰ、Ⅲ型胶原蛋白降低(P<0.05),TGF-β1及p-smad2和p-smad3蛋白表达下调(P<0.05或P<0.01)。结论运动改善T2DM大鼠心肌纤维化,抑制TGF-β1的表达和smad2/3的磷酸化,TGF-β1/smad可能是运动抑制T2DM大鼠心肌纤维化的重要信号通路。

Objective To investigate the effects of exercise on the myocardial fibrosis of diabetic rats and discussed the role of TGF-βl/smad signaling pathways in the process. Methods Type 2 diabetic rat model was established by streptozotocin injection through abdominal cavity and high fat diet. Then all the diabetic rats were divided into three groups： control group （NC）, diabetes group （T2DM） and diabetes exercise group （T2DME）. NC and T2DM group were kept quiet for 8 weeks. T2DME group was trained for 8 weeks. After the excercise, weight and blood glucose were measured. Collagen levels was observed by Sirius red staining. The degree of myocardial fibrosis was evaluated by collagen volume fraction（CVF）. Collagen I and Ⅲ was detected by immunofluorescent staining. TGF-β1, smad2, p-smad2, mad3 and p-smad3 were measured by western blot. Results Weight decreased [（528±71） vs （362±33）g,P〈 0. 05],blood sugar increased [（6.4±3.8） vs （26.0±7.5）retool/L）,P〈0. 01], CVF increased [（2.2±0. 31）% vs （5.8±0.45）%,P〈0. 01], collagen I and Ⅲ increased （P〈0.05 or P〈0. 01）,TGF-β1, P-smad2 and P-smad3 protein expression increased significantly （P〈0.05 or P〈0.01） in T2DM group than in control group. Blood glucose decreased [（26. 0±7. 5） vs （21.0±6.8）mmol/L） ,P〈0. 05],CVF decreased [（5.8±0.45）% vs （3. 6±0. 33%）, P〈0. 05], collagen I and HI decreased （P〈0.05）,TGF-β1, P-smad2 and P-smad3 protein expression were down-regulated significantly （P 〈0.05 or P〈 0.01） in T2DME group than in T2DM group. Conclusion Myocardial fibrosis in diabetes rats is inhibited, the expression of TGF-β1 and smad2./3 phosphorylation is down-regulated by exercise. TGF-β1/smad may be an important signaling pathway in this process.