小胶质细胞P2X7信号通路介导室旁核OT和AVP能神经元敏感化参与急性心肌梗死的调控机制

项目名称： 小胶质细胞P2X7信号通路介导室旁核OT和AVP能神经元敏感化参与急性心肌梗死的调控机制

项目编号： No.31271215

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 朱大年

作者单位： 复旦大学

项目金额： 85万元

中文摘要： 急性心肌梗死发病率及死亡率呈逐年上升趋势，其发病机制复杂且缺乏特异性的治疗措施。我们最近的研究发现急性心肌梗死激活了下丘脑室旁核内小胶质细胞并伴随有膜蛋白P2X7的高表达，其对急性心肌梗死的调控机制未见报道。本课题在已有研究的基础上，拟采用大鼠、P2X7-/-小鼠急性心肌梗死模型为研究对象，结合在体及离体实验，应用基因敲除、si-RNA、脑核团微量注射、蛋白免疫印迹、RT-PCR、免疫组化、膜片钳、细胞外记录神经放电、HLPC等电生理及分子生物学手段，以小胶质细胞P2X7受体蛋白激活后释放的炎性细胞因子IL-1β为研究切入点，从不同角度深入探讨小胶质细胞P2X7受体蛋白对OT及AVP能神经元敏感化的分子机制及神经信号网络。阐明室旁核小胶质细胞P2X7受体对急性心肌梗死大鼠外周交感神经紧张性及心功能的神经调控及分子作用机理，以期为急性心肌梗死的治疗提供新的药物作用靶点和理论依据。

中文关键词： 急性心肌梗死；下丘脑室旁核；小胶质细胞；P2X7受体；加压素和催产素能神经元

英文摘要： The mortality and incidence of acute myocardial infarction (AMI) showed a trend of escalation year by year. Furthermore, the pathogenesis of AMI is complicated and the special therapeutic strategy for AMI is insufficient. In our previous study, we demonstrate that the microglia in hypothalamic paraventricular nucleus were activated induced by AMI and the expression of P2X7 receptor protein was up-regulated in time-dependent manner in the progress of AMI. So far, the regulative mechanism of the P2X7 receptor on AMI induced by myocardial ischemia has not been reported. Based on our previous study, we would adopt AMI animal model of rats and P2X7-/- mouse as research object, combining with in vivo and in vitro experiment, to investigate the molecular and neural regulative muchanism of P2X7 receptor on vasopressin (AVP) and oxytocin (OT) neurons sensitization. In order to explorate the neural signaling network involved in the regulative effects of P2X7 receptor on AMI, we consider inflammatory cytokines IL-1βas research access and adopte multiple electrophysiological, molecular experimental research methods such as gene knockout, si-RNA, brain area microinjection, westernblot, RT-PCR, immunohistochemistry, patch-clamp, extracellular nerve discharges recording and HLPC. This research would clarify the the neural and

英文关键词： acute myocardial infarction；hypothalamic paraventricular nuleus；microglia；P2X7 receptor；vasopressin and oxytocin neurons