利用条件性敲除RBP-J的心脏祖细胞研究Notch信号通路在增强干细胞心脏修复中的作用

我们前期工作观察到激活Notch信号通路能够促进心脏祖细胞（CPCs）分化，改善急性心肌梗死（AMI）的心功能及减少梗死面积，但其机制尚不清楚。我们假设Notch信号途径通过SDF-1/CXCR4轴信号转导，进一步调节下游P38MAPK 及Erk1/2的磷酸化，促进CPCs在缺血环境中的生存，旁分泌调节受损心肌细胞,从而增强心脏修复。本研究利用腺病毒介导转染N1ICD直接激活CPCs的Notch信号通路，及条件性敲除Notch信号通路中关键性的转录因子RBP-J,使Notch信号完全失活， 探索RBP-J介导的Notch信号通路对CPCs自身增殖，凋亡及旁分泌影响受损心肌的调控机制。SDF-1/CXCR4,P38 MAPK/Erk1/2信号通路为主要指标，明确RBP-J依赖的Notch信号通路是机体内源性抗凋亡机制，以期探寻提高临床CPCs移植治疗AMI疗效的新机制。

Our previous study suggested that activation of the Notch signaling pathway can promote the differentiation of cardiac progenitor cells (CPCs) to improve the heart function post myocardial infarction (AMI) and to reduce infarct size, but its mechanism is largly unknown. we hypothesized that Notch signaling pathway through SDF-1/CXCR4 axis signal transduction further to adjust downstream P38MAPK and Erk1 / 2 phosphorylation, and promote the survival of CPCs in the ischemic environment, and paracrine regulation of damaged myocardial cells, thereby enhancing cardiac repair . In this study, adenovirus-mediated transfection N1ICD direct activation of the Notch signaling pathway in CPCs, and conditional knockout RBP-J-critical transcription factor of Notch signaling , completely inactivated Notch signaling, and explore the role of RBP-J-mediated Notch signaling pathway in CPCs proliferation, apoptosis and paracrine regulation mechanisms affect the damaged myocardium. SDF-1/CXCR4, P38 MAPK/Erk1/2 signaling pathway as the main indicators, to explore the new mechanisms and new prevention strategies for stem cell based heart repair.