阿托伐他汀激活自噬促进急性心肌梗死后间充质干细胞存活率和移植疗效的机制研究

In order to investigate the mechanism of atorvastatin promoted the survival and therapeutic effect of mesenchymal stem cells (MSCs) after transplantation in post infarct heart, according to our previous studies, we assume that atorvastatin could protect mesenchymal stem cells from apoptosis via autophagy activation through AMPK/mTOR pathway. We establishe the hypoxia/serum deprivation model of MSCs, and make the autophagy-related gene beclin1 silence and overexpression through transfection techonology to observe the effect of statin on MSCs autophagy and apoptosis. Meanwhile, we establish rat AMI models and transplant normal MSCs , beclin1 silence MSCs, beclin1 overexpression MSCs 30min after AMI. Atorvastatin and AMPKinhibitor are also used. All animals will get echocardiogram on the first and fouth week after AMI operation. After echocardiogram the myocardial tissue will be used for histologu and molecular-biology analysis in purpose of testifying our hypothesis. This original investigation is novelty designed and has great clinical meaning.

为进一步明确他汀激活自噬促进急性心肌梗死后移植间充质干细胞（MSCs）存活和移植疗效及相关机制，本项目基于我们前期实验的结果，假设阿托伐他汀通过AMPK/mTOR信号通路激活自噬，抑制急性心肌梗死后缺血缺氧环境诱导的MSCs凋亡从而发挥其心脏保护作用。拟通过体外大鼠MSCs培养，建立缺氧/无血清模型模拟体内缺血缺氧心肌微环境。通过观察自噬相关基因beclin1沉默及过表达，研究自噬在缺氧/无血清诱导MSCs凋亡中的作用以及他汀激活自噬保护MSCs的相关信号通路。同时拟以SD大鼠为研究对象，建立AMI模型，建模30分钟后移植正常MSCs以及beclin1基因沉默或过表达的MSCs，并给予相应的阿托伐他汀、AMPK信号通路抑制剂处理，分别于心梗造模后1周及4周行超声心动图评价心功能，取材左室心肌行组织学和分子生物学检测，可望证明上述假设。本研究原创性突出，设计新颖，具有重要的临床意义。