以羊水为媒介的“母婴信息传递”在调控成年心肌细胞增殖中的作用和机制研究

心肌细胞丢失是心肌梗死后心衰发生的重要物质学基础，成年心肌细胞微弱的增殖能力为心脏修复提供了希望。尽管成年心肌细胞增殖能力锐减的原因不清楚，脱离母体内环境是该病理生理过程发生的关键时间点，我们以“母婴信息传递”的关键介质—“羊水”为研究对象，发现了羊水具有促心肌细胞增殖能力，并在动物实验上显示了其对心梗的修复效果。预实验显示羊水中蛋白质、RNA均在促心肌增殖中扮演重要角色，筛选实验发现了数个具有促增殖能力的候选蛋白。进一步的研究显示了羊水在促心肌细胞增殖基因表达的同时，也改变了与增殖有关的组蛋白修饰状态，据此，我们提出 “母婴信息传递在心肌细胞增殖中发挥重要作用，羊水是母婴信息传递的关键介质；对心肌增殖基因和增殖表观修饰模式的双重调控是其发挥作用的关键机制”的假说，该研究将从母婴信息传递的角度发掘心肌增殖的关键动力，有望为成年心脏再生提供新的治疗策略。

Cardiomyocyte loss is an important basis for heart failure after myocardial infarction and the weak proliferative capacity of adult cardiomyocyte provides hope for cardiac repair. The mechanism for the sharp decline in the proliferative capacity of cardiomyocyte after birth is unclear, and the departure from the maternal environment is a key time point for the pathophysiological process. We used the key media of "maternal-infant material transport", amniotic fluid, as the research object and found amniotic fluid promoted cardiomyocyte proliferation in vitro, which was supported by our in-vivo experiment, amniotic fluid improved cardiac function with increased cardiomyocyte proliferation after myocardial infarction. Preliminary experiments showed that both protein and RNA in amniotic fluid had the promoting effect on cardiomyocyte proliferation and several candidate proteins have been discovered. Our study further found amniotic fluid not only promoted the expression of myocardial proliferative genes, but also changed the histone modification status of cardiomyocyte. Based on these evidences, we speculated that maternal-infant material transport plays an important role in cardiomyocyte proliferation and during which amniotic fluid is the key mediator; dual regulation of myocardial proliferative genes and epigenetics is the key mechanism. This study will provide a new view to explore effective strategies to promote adult cardiomyocyte proliferation.