哺乳动物新生期心肌细胞增殖及其调控机制研究

心血管疾病严重威胁人类健康，其根本原因是心肌细胞的丢失，因此心肌细胞再生研究是近年来的研究热点。前期研究认为心肌细胞的更新主要通过自我增殖完成；新生期心肌细胞具有一定增殖能力，但随着年龄增长逐渐减弱，成体心肌细胞几乎不具有增殖能力。近期报道称，gp130基因在心脏损伤修复中参与调控心肌细胞的增殖。据此，申请人提出科学问题：新生期心肌细胞增殖的动态变化是怎样的，心肌细胞增殖的分子调控机制是什么。本研究拟利用一种可以长时间不间断捕捉细胞增殖的新技术-ProTracer来绘制新生期心肌细胞的增殖图谱，分析新生期心肌细胞的细胞分裂、多核化和多倍体化情况，研究gp130基因在新生期心肌细胞增殖中的作用。以上科学问题的解决有望为进一步阐释心肌细胞的增殖受阻和激活心脏再生提供新的线索和依据。

Cardiovascular disease is a serious threat to human health, and the loss of cardiomyocytes is a fatal factor. Therefore, cardiomyocytes regeneration has been a significant research in recent years. Previous studies have revealed that new cardiomyocytes are generated through self-proliferation. Neonatal cardiomycytes can regenerate by proliferation, while the proliferation ability of neonatal cardiomyocytes gradually reduced after birth; cardiomyocytes of adult heart can hardly proliferate. It has recently been reported that gp130 gene is involved in regulating the proliferation of cardiomyocytes during heart regeneration. Based on this, the applicant try to illustrate the dynamics of neonatal cardiomyocytes proliferation, and focus on the molecular mechanism of cardiomyocytes proliferation. To attain these aims, this study plans to investigate neonatal cardiomyocytes proliferation by ProTracer that permits temporally seamless genetic recording of cell proliferation events and to clarify the cell division, multinucleation and polyploidysation. This study also focuses the role of gp130 gene in neonatal cardiomyocytes proliferation during homeostasis. The results of this study can provided new ideas and targets for cardiomyocytes proliferation and cardiac regeneration.