亚低温治疗改善肾上腺素通过β受体-G蛋白信号通路致复苏后心功能障碍的机制研究

项目名称： 亚低温治疗改善肾上腺素通过β受体-G蛋白信号通路致复苏后心功能障碍的机制研究

项目编号： No.81460289

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 宋凤卿

作者单位： 广西医科大学

项目金额： 49万元

中文摘要： 肾上腺素仍是目前心肺复苏的首选用药。但众所周知，肾上腺素在提高自主循环恢复的同时可通过其β受体信号通路增加复苏后的心功能障碍，给早期复苏成功的心脏骤停患者带来负面影响。我们前期研究发现：心肺复苏时给予低温干预，应用肾上腺素后可减轻复苏后的心功能障碍，进而改善远期存活，但其机制尚不清楚。本研究拟在此基础上，建立大鼠心脏骤停模型，给予亚低温干预，心肺复苏时应用肾上腺素后，以蛋白印迹法、激光共聚焦显微镜等方法，检测复苏后不同时点心肌β1受体密度的变化，G蛋白水平、cAMP含量、PKA活性、钙超载以及心肌的炎症因子、细胞凋亡及相关蛋白mRNA的变化等，探讨低温干预改善肾上腺素在心肺复苏疗效的机制是否通过抑制或阻断β受体-G蛋白信号通路、减轻炎症反应、减少钙超载及凋亡,为心肺复苏时合理应用肾上腺素进而改善临床心肺复苏远期疗效提供一条新思路。

中文关键词： 亚低温；肾上腺素；心肺复苏；心功能障碍；信号通路

英文摘要： Epinephrine is still the first choice of drug for cardiopulmonary resuscitation (CPR). Although it increases the restoration of spontanous circulation, it also induces postresuscitation myocardial dysfunction through its βreceptor signaling pathways, which can result in an adverse outcome for cardiac arrest patients.In a previous study, we found that therapeutic hypothermia during CPR, improved the epinephrine-induced myocardial dysfunction and then increased long term survival. However, the mechanism of action is still unknown. In this project, we will establish a cardiac arrest model in rat with therapeutic hypothermia. The β1 receptor, G protein, cAMP, PKA，calcium overload and inflammatory factors will be tested in myocardial tissue using Westen Blot, laser scanning confocal microscopy et al.at different time points. These measurements will determine the extent to which downregulation of the β1 receptor density, alleviation of the inflammatory response, reduction of calcium overload, and apoptosis contribute to the mechanism of hypothermia improvement in epinephrine-induced postresuscitation myocardial dysfunction, and will provide new ideas for epinephrine administration in CPR.

英文关键词： Hypothermia;Epinephrine;Cardiopulmonary resuscitation;Myocardial dysfunction;Signaling pathway