摘要
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 study the effect of combined valsartan-mesenchymal stem cells （MSCs） thera- py on diabetic cardiomyopathy and to explore the possible underlying mechanisms. Methods： High-fat high-sugar diet and low dosage streptozotoein （STZ） were used to establish a rat model of type 2 diabetic cardiomyopathy, and GFP-labeled BMSCs were constructed in vitro so as to facilitate tracing. After the modeling, valsartan orally and BMSCs transplantation were given respectively or collectively. Four weeks after the modeling, we detected the cardiac function, myocardial fibrosis and myocardial apoptosis of different groups, and MMP/TIMP expression and CTGF was analyzed by Western-blotting. Results： The model group showed a decreased cardiac function and microvascular density and increased myocardial fibrosis and rate ot apoptosis, while after treatment, cardiac function and microvessel density increased, myocardial fibrosis and apoptosis rate decreased, and the combination group has a better result than that of valsartan or BMSCs treatment group （P〈0.05）. In the model rat, MMP-9 and CTGF increased, and TIMP-1 decreased （P〈0.05）, after treatment, pure valsartan group has a lowered CTGF （P〈0.05）, BMSCs transplant group showed increased microvascular density, decreased MMP-9 level, and increased TIMP-1. In the combined group, MMP-9 decreased, TIMP-1 increased, and CTGF declined, and the difference was statistically significant as compared with any of the valsartan/ MSCs treatment groups and control group （P〈0.05）. Conclusion： Combination of valsartan and BMSCs transplantation shows a synergistic effect, significantly improves the cardiac function of diabetic cardiomyopathy, induces angiogenesis, and inhibits myocardial remodeling.
出处
《武汉大学学报（医学版）》
CAS
北大核心
2013年第1期71-75,94,共6页
Medical Journal of Wuhan University
基金
武汉市卫生局基金资助项目(编号:武卫[2007]43号)
