青春期前小鼠心肌细胞经历了短暂的爆发性增殖，此过程与甲状腺激素及 IGF-1/Akt 信号通路有关。多种心脏损伤模型的研究证实新生小鼠心肌有再生潜能；但这种潜能局限于短暂的时间窗，调控机制尚不完全清楚。T3 通过甲状腺激素受体调控 IGF-1 的表达；IGF-1 通过激活 PI3K/Akt 信号通路调控细胞的生长、增殖、分化、凋亡和存活。前期试验发现 T3 预处理显著增加缺血模型下新生小鼠心肌细胞磷酸化 IGF-1R 的表达。本项目拟用野生型及诱导性心肌细胞特异 IGF-1R 基因敲除小鼠为试验对象，观察 IGF-1 及其介导的信号通路关键分子在小鼠心脏发育不同时间点表达的变化及与心肌细胞增殖的关系；观察 IGF-1 介导的信号通路体外对不同条件下 T3 预处理的心肌细胞增殖及凋亡的影响，并阐明其机制；进一步探讨体内调控 IGF-1 介导的信号通路能否改善梗死后心肌细胞再生的潜能。

Recent study shows that in mice during preadolescence, cardiomyocytes undergo a burst of proliferation that is related to a thyroid hormone surge. Several independent groups prove that neonatal mouse heart has the transient capacity to regenerate after injury, however, the regulating mechanisms are still not clear.T3 regulates IGF-1 mRNA expression, and IGF-1 regulates cell growth, proliferation, differentiation, apoptosis and survival through PI3K/Akt pathway. Our preliminary study shows that pretreatment with T3 significantly upregulats p-IGF1R expression of cardiomyocytes. Using the inducible deletion of IGF-1R in mice cardiomyocyte model, we will investigate the involvement of specific IGF-1 pathway proteins in the developing hearts. We will investigate the effects and mechanisms of IGF-1 pathway on cardiomyocyte proliferation under different conditions. Finally, we will examine whether manipulating IGF-1 pathway can improve the regeneration efficiency of neonatal mouse heart after injury. This study could lead to new strategies for cardiac repair.