骨髓间充质干细胞联合螺内酯抑制糖尿病心肌病大鼠细胞凋亡的机制研究

Study on the mechanism of bone marrow mesenchymal stem cells combined with Spironolactone in inhibiting myocardial apoptosis in rats with diabetic cardiomyopathy

目的:探讨骨髓间充质干细胞联合螺内酯抑制糖尿病心肌病心肌纤维化的可能机制。方法:建立糖尿病心肌病大鼠模型:SD大鼠随机分为对照组与模型组,对照组普通喂养,模型组通过小剂量链脲佐菌素(STZ)及高糖高脂饲养。通过超声、血流动力学、病理染色等评判模型。将构模成功的模型大鼠随机分为3组予以饲养:PBS组(尾静脉注射PBS),干细胞组(干细胞移植),联合组(干细胞移植及螺内酯灌胃)。通过Western Blot检测各组大鼠14-3-3蛋白的表达。结果:(1)通过血糖、血脂、心脏指数、心脏超声及血流动力学检测,判断糖尿病心肌病模型成功;(2)免疫荧光及流式细胞学检测证实干细胞移植到模型大鼠体内;(3)干细胞组及联合组的心肌纤维化要低于PBS组,而14-3-3蛋白表达较PBS组明显上升(均P<0.05),联合组更为明显。结论:骨髓干细胞通过上调14-3-3蛋白表达抑制糖尿病心肌病的心肌纤维化,和螺内酯有协同作用。

Objective：To study the mechanism of bone marrow mesenchymal stem cells （BMSCs） combined with Spironolactone in inhibiting myocardial apoptosis and fibrosis in diabetic cardiomyopathy. Method：The model rats were treated by intraperitoneal injection with streptozocin and then fed with high glucose and lipid diet. The controls were fed with standard diet. The animal models were evaluated by ultrasound, hemodynamic and pathological staining. The diabetic cardiomyopathy rats were divided into PBS group, stem cell group, and combination group （stem cell transplantation and intragastrie administration of Spironolactone）. The expression of 14 3-3 pro- tein was detected by Western-Blot. Result： （1）The successful establishment of diabetic cardiomyopathy rat model was confirmed by the detection of blood glucose, blood lipid, echocardiography and hemodynamics. （~）The analysis of immunofluorescenc proved the successful transplantation of BMSCs. ③Compared to PBS group, the cardiomyo cyte apoptosis in stem cell group and combination group was lower than that in PBS group, but the expression of 14-3-3 protein increased significantly, especially in combination group （all P〈0.05）. Conclusion： BMSCs transplantation could prohibit the cardiomyocyte apoptosis in diabetic cardiomyopathy by up-regulating the expression of 14-3-3 protein. Combination with Spironolactone showed a significant synergistic effects.