基因修饰的干细胞移植治疗急性心肌梗死(AMI)效果显著，由于缺乏安全高效的基因传递系统，临床运用受限。研究表明，金属蛋白酶组织抑制因子-1(TIMP -1)通过抑制基质金属蛋白酶家族(MMPs)表达，具有抗细胞凋亡和抗心肌纤维化的作用。本研究尝试用超声微泡-基因-细胞传递体系，对干细胞移植治疗中的关键问题进行有意义的探索：拟①制备携TIMP-1超声微泡-阳离子纳米脂质体复合物，将TIMP-1转染入骨髓间充质干细胞(MSCs)；②经静脉注射混合了超声微泡的基因修饰MSCs(TIMP-1- MSCs)，以超声辐照缺血心肌，通过超声靶向微泡破坏(UTMD)促进TIMP-1- MSCs靶向归巢、分化，并通过高表达TIMP-1，抑制MMPs表达，最终达到补充心肌内有效收缩单元、减少细胞凋亡、促进新生血管生成、减少或逆转心肌纤维化的目的；③利用超声生物显微镜技术评价治疗后小鼠左室构型及心肌力学特征。

Mesenchymal stem cells (MSCs) transplantation is a very promising method to treat acute myocardial infarction(AMI) and has gained significant attention now days. However, little effect of it on AMI. Therefore, novel approaches are needed to augment the efficacy by which transplanted MSCs enhance cardiac repair in order to optimize cardiac regain of function following cell transplantation therapy. Research have showed that tissue inhibitors of metalloproteinase-1(TIMP-1) is innate protease inhibitors of matrix metalloproteinases(MMPs), which play a fundamental role in the degradation and aberrant production of ECM proteins. We want to transfect MSCs with TIMP-1, an antiapoptotic and antifibrotic gene, transplant them into the myocardium post-MI, and evaluate their effects on cardiac myocyte engraftment and differentiation, myocardial remodeling and cardiac function. We plan to:①combine ultrasound microbubbles with cationic nanoliposomes by biotin-avidin system and prepare a new type of gene vector. Use ultrasound-targeted microbubble destruction (UTMD) to increase the permeability of capillaries, so that it can mediate transfection of MSCs with TIMP-1(TIMP-1- MSCs);②inject microbubbles and TIMP-1- MSCs cells to the ischemic cardiac region in the AMI animal model through the tail vein. Promote stem cells homing by UTMD, so that they can over-express TIMP-1, following transplantation into the infracted myocardium. It will increase angiongenesis and new myocardium formation, and attenuate ventricular remodeling by inhibiting both interstitial and vascular fibrosis;③ Left ventricular configuration and myocardial function after treatment was evaluated using high resolution ultrasound biological microscope technique.