TIMP-1和Ang-1基因修饰的BMSC输注对心肌梗死后大鼠心功能的影响  

TIMP-1 and Ang-1 gene-modified BMSCs transplantation to improve cardiac function of rats with myocardial infarction

作　　者：李杰[1] 吴华[1] 李大为[1] 王浩然[1] 蒋树林[1] 

机构地区：[1]哈尔滨医科大学附属第二医院,150086

出　　处：《中华器官移植杂志》2016年第9期556-560,共5页Chinese Journal of Organ Transplantation

基　　金：黑龙江省教育厅科学技术研究面上项目（11541118）

摘　　要：目的探讨基质金属蛋白酶组织抑制因子（TIMP-1）和血管生成素（Ang-1）基因修饰骨髓间充质干细胞（BMSC）输注对心肌梗死大鼠左心功能的影响。方法以携带人T1MP1和（或）Ang-1基因的质粒转染BMSC。结扎Wistar大鼠左冠前降支，制作急性心肌梗死模型。模型大鼠分为TIMP1-BMSC组、Ang-1-BMSC组、TIMP1＋Ang-1-BMSC组和Mock-BMSC组，分别于梗死区周边注射相应基因转染后的BMSC悬液；以只注射无血清培养液的模型大鼠为对照组。4周后用超声心动图检测左心功能，免疫组织化学染色检测交界区心肌凋亡、胶原含量和新生血管密度。结果BMSC输注后4周，TIMP1＋Ang-1-BMSC组心功能明显改善，左心室射血分数为（58．0±2．6）％，短轴缩短率为（43．3±1．5），均高于对照组和Mock-BMSC组（P〈0．05）；与对照组和Mock-BMSC组相比较，TIMP1＋A时1-BMSC组交界区心肌凋亡减轻、胶原含量减低、毛细血管密度增加（均P〈0．05）。结论TIMP1＋An手1转基因修饰的BMSC输注可显著改善心肌梗死后大鼠心脏功能，其机制可能与交界区血液循环改善，心肌凋亡减少，心肌梗死后左心室重构减轻有关。Objective To evaluate the effects of TIMP-1 and Ang-1 gene-modified BMSCs transplantation on the left ventricular function of rats with myocardial infarction. Methods The rat BMSCs were transfected with eukaryotie expression plasmid encoding TIMP-1 or/and Ang-1 gene by liposome. Acute myocardial infarction was made in male rats by ligation of the left anterior descending （LAD） coronary artery. BMSCs carrying TIMP-1 or/and Ang-1 gene were injected into the ischemic myocardium after LAD ligation. Four weeks after the administration, cardiac function was assessed by echocardiography and the hearts were harvested and sectioned for immunohistochemistry to examine the apoptosis, the collagen content and angiogenesis density. Results TIMP-1 and Ang-1 genemodified BMSCs transplantation significantly improved the cardiac function, myocardial apoptosis was alleviated, collagen content decreased and the angiogenesis density in border-zone was increased significantly （P〈0. 05）. Conclusions The results suggest that the combination of TIMP-1 and Ang-1- gene modified BMSCs transplantation can improve the cardiac function of rats with myocardial infarction. The increase of the blood supply, the alleviation of myocardial apoptosis and ventricle remolding after myocardial infarction possibly play important roles in the mechanism.

关 键 词：间充质干细胞移植 基因修饰 基质金属蛋白酶抑制因子 血管生成素 心肌梗塞 治疗 大鼠 

分 类 号：R542.22[医药卫生—心血管疾病]