心肌干细胞旁分泌肝细胞生长因子对心肌梗死大鼠心电生理影响的机制研究

Myocardial infarction is a serious disease threatening to human health. At present, the main treatments can improve the survival rate and life quality to patients with myocardial infarction. However, the mortality remains high. It is necessary to find a new effective treatment. With the development of the biological engineering, cardiac stem cell (CSC) transplantation is a promising treatment to myocardial infarction. Our previous experiments proved that CSC transplantation can improve the electrophysiological characteristics in rats with myocardial infarction. However, the mechanisms remain unclear. Other experiments show that CSC can heal the myocardial infarction model by paracrine mechanisms, in which hepatocyte growth factor (HGF) paracrined by CSC can alleviate the myocardial fibrosis. Moreover, myocardial fibrosis is an important factor of arrhythmia. Based on the above points, in this item, myocardial fibrosis as the point of penetration, we investigate the effects and mechanisms of HGF paracrined by CSC transplantation on the cardiac fibroblasts (CFS), and observe the effects of the changes of CFS and myocardial fibrosis on cardiac electrophysiology, so as to demonstrate the mechanisms of the healing effects. This experiment will provide the theoretical basis for the future application of CSC transplantation and the experimental support for discovering new drug targets.

心肌梗死是一种严重威胁人类健康的疾病。现阶段，主流治疗手段能够提高心肌梗死患者的生存率和生活质量，但死亡率仍然较高，有需要寻找新的治疗手段。随着生物工程学发展，心肌干细胞（CSC）移植是一种有前景的治疗方法。我们前期实验证实：移植CSC治疗心肌梗死大鼠，可以改善其心电生理特性，然而CSC改善心电生理特性的机制尚不明确。实验证实，CSC可以通过旁分泌机制对心肌梗死模型修复，其中肝细胞生长因子（HGF）可以明显改善心肌梗死心脏纤维化；而心脏纤维化已经被证实是导致心律失常的重要因素。所以本项目以心肌纤维化为切入点，研究移植CSC通过旁分泌HGF对心肌成纤维细胞（CFS）的作用及其机制，观察CFS及心肌纤维化的改变对心电生理的影响，从而探讨移植CSC旁分泌HGF对心肌梗死大鼠心电生理影响的机制。为CSC移植日后应用提供理论依据，并为发掘新的药物靶点提供实验支持。

心肌梗死是一种严重威胁人类健康的疾病。现阶段，主流治疗手段能够提高心肌梗死患者的生存率和生活质量，但死亡率仍然较高，有需要寻找新的治疗手段。随着生物工程学发展，心脏干细胞（CSC）移植是一种有前景的治疗方法。我们前期实验证实：移植CSC治疗心肌梗死大鼠，可以改善其心电生理特性，然而CSC改善心电生理特性的机制尚不明确。实验证实，CSC可以通过旁分泌机制对心肌梗死模型修复，其中肝细胞生长因子（HGF）可以明显改善心肌梗死心脏纤维化；而心脏纤维化已经被证实是导致心律失常的重要因素。所以本项目以心肌纤维化为切入点，研究移植CSC通过旁分泌HGF对心肌成纤维细胞（CFS）的作用及其机制，观察CFS及心肌纤维化的改变对心电生理的影响。本研究结果显示：CSC旁分泌HGF在CSC移植改善心肌梗死模型心肌纤维化及心电生理特性起重要作用。HGF可通过激活c-Met/PI3K/Akt通路发挥抗纤维化作用。此研究结果为CSC移植日后应用提供理论依据，并为发掘新的药物靶点提供实验支持。