力-电微环境增强Pim-1诱导心肌祖细胞分化、增殖在梗死后心肌修复和重构中的作用及其机理研究

A large number of cardiomyocyte necrosis and apoptosis has been associated with myocardial infarction (MI), thereby causing the structure and function of ventricular remodeling,which leading to the heart failure occurrence and development. Studies have shown that Necrosis and apoptosis of cardiomyocyte are irreversible,however, mitotic can occur temporarily and low efficiency in the part of cardiomyocyte at the border of infarcts. High-level expressed Pim-1 will be able to inhibit the apoptosis and promote the "homing" of cardiac progenitor cells (CPCs).But It is difficult to reach the cells level required by cardiac repairing after MI. In this study, based on multidisciplinary research, intending to build a micro-environment of a three-dimensional space composed by force, electrical and biochemical stimuli and control the local Pim-1 expression levels,to observe the effective of Pim-1that inhibit cardiomyocyte apoptosis and stimulate differentiation and proliferation of CPCs.Also to explore the inhibition of cardiomyocyte apoptosis of Pim-1 and its signal transduction mechanisms . And then collect the ECG signals in vivo animal experiments, Gated stimulated myocardial will be achieved after the signals analysis and conversion.The process and its mechanism of electromechanical- biological homology coupling between the cultured myocardial tissue and the target myocardial tissue will be explored. New biological evidence and theoretical basis is expected to provide for the treatment of heart failure after MI.

心肌梗死（MI）后伴随心肌细胞大量坏死或凋亡，进而引起心室结构和功能重构，导致心力衰竭发生和发展。研究表明，已坏死或进入凋亡程序的心肌细胞无法逆转，但梗死交界区域的部分心肌细胞可发生暂时、低效率的有丝分裂增殖。高水平表达的 Pim-1有抑制细胞凋亡，促进心肌祖细胞（CPCs ）"归巢"的现象。单一因素作用下CPCs"归巢"分化难以达到心肌损伤后修复所需的细胞数量等级。本研究基于多学科交叉层面研究，拟构建一个集力、电和生物化学刺激的三维空间微环境并控制局部Pim-1表达水平，观察 Pim-1抑制心肌细胞凋亡，刺激CPCs定向分化和增殖作用；并初步探索Pim-1抑制心肌细胞凋亡的作用及其信号传导机制；进而通过在体动物实验，采集心电信号分析转换后实现门控刺激培养心肌，探索培养心肌组织和目标心肌组织之间的力-电-生物同源性耦合过程及其机制。可望为MI后心力衰竭的治疗提供新的生物学证据和理论基础。

心肌梗死（MI）后伴随心肌细胞大量坏死或凋亡，进而引起心室结构和功能重构，导致心力衰竭发生和发展。研究表明，已坏死或进入凋亡程序的心肌细胞无法逆转，但梗死交界区域的部分心肌细胞可发生暂时、低效率的有丝分裂增殖。高水平表达的 Pim-1 有抑制细胞凋亡，促进心肌祖细胞（CPCs ）"归巢"的现象。单一因素作用下 CPCs"归巢"分化难以达到心肌损伤后修复所需的细胞数量等级。本研究基于多学科交叉层面研究，拟构建一个集力、电和生物化学刺激的三维空间微环境并控制局部 Pim-1 表达水平，观察 Pim-1 抑制心肌细胞凋亡，刺激 CPCs 定向分化和增殖作用；并初步探索 Pim-1 抑制心肌细胞凋亡的作用及其信号传导机制；进而通过在体动物实验，采集心电信号分析转换后实现门控刺激培养心肌，探索培养心肌组织和目标心肌组织之间的力-电-生物同源性耦合过程及其机制。可望为 MI 后心力衰竭的治疗提供新的生物学证据和理论基础。