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目的:评价联合给予缬沙坦和骨髓间充质干细胞(BMSCs)治疗糖尿病心肌病的疗效及可能机制。方法:用高脂高糖饮食及小剂量链脲佐菌素(STZ)建立2型糖尿病心肌病大鼠模型,体外构建绿色荧光蛋白(GFP)标记的BMSCs便于示踪。造模成功后,单独及联合给予缬沙坦灌胃和BMSCs移植。4周后检测不同组大鼠心功能、心肌纤维化及心肌凋亡,免疫印迹方法分析基质金属蛋白酶(MMP)/金属蛋白酶组织抑制剂(TIMP)及结缔组织生长因子(CTGF)的表达。结果:模型组大鼠心功能及微血管密度下降,心肌纤维化及凋亡比率增加,处理后,心功能及微血管密度升高,心肌纤维化及凋亡率下降,联合组优于单独处理组(P<0.05)。模型组大鼠心肌MMP-9增高,TIMP-1下降,CTGF上调(P<0.05),处理后,单纯缬沙坦组CTGF下调(P<0.05),BMSCs移植组可见标记的BMSCs定植分化为新生血管,且MMP-9下降,TIMP-1增高。联合组MMP-9下降,TIMP-1升高,CTGF下降,且与单纯组及对照组差异具有统计学意义(P<0.05)。结论:联合缬沙坦和骨髓间充质干细胞能明显改善糖尿病心肌病大鼠心功能,诱导血管新生,改善心肌重构,具有协同作用。
Objective: To evaluate the efficacy and possible mechanism of valsartan and bone marrow mesenchymal stem cells (BMSCs) in the treatment of diabetic cardiomyopathy. Methods: A rat model with type 2 diabetic cardiomyopathy was established by high fat and high glucose diet and low dose of streptozotocin (STZ), and labeled with green fluorescent protein (GFP) in vitro. After successful modeling, valsartan and BMSCs transplantation were given alone and in combination. After 4 weeks, cardiac function, myocardial fibrosis and myocardial apoptosis were detected in different groups of rats. Expression of matrix metalloproteinase (MMP) / tissue inhibitor of metalloproteinase (TIMP) and connective tissue growth factor (CTGF) was analyzed by Western blotting. Results: In the model group, heart function and microvessel density decreased, myocardial fibrosis and apoptosis rate increased. After treatment, cardiac function and microvessel density increased, myocardial fibrosis and apoptosis rate decreased, and the combination group was better than the single treatment group P <0.05). After treatment, the CTGF of valsartan group was down-regulated (P <0.05). The labeled BMSCs in the BMSCs transplantation group were colonized and differentiated into newborn Vascular, and MMP-9 decreased, TIMP-1 increased. MMP-9 decreased, TIMP-1 increased and CTGF decreased in the combined group, and there was significant difference between the combined group and the control group (P <0.05). CONCLUSION: Combination of valsartan and bone marrow mesenchymal stem cells can significantly improve cardiac function, induce angiogenesis and improve myocardial remodeling in diabetic cardiomyopathy with synergistic effect.