一氧化碳可逆性抑制线粒体电子传递链保护复苏后心肌功能的机制研究

项目名称： 一氧化碳可逆性抑制线粒体电子传递链保护复苏后心肌功能的机制研究

项目编号： No.81460288

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： 王晓红

作者单位： 宁夏医科大学

项目金额： 47万元

中文摘要： 一氧化碳（CO）有抗炎、抗氧化、抗凋亡等多重保护效应，是重要气体信使。我们前期研究证实诱导内源性CO产生可有效保护大鼠复苏后心功能和缺氧复氧损伤心肌细胞，且明显保护心肌线粒体的完整性和再复氧期线粒体有氧呼吸功能，但其保护机制未明。CO仅于低氧环境结合线粒体呼吸复合酶IV，我们首次提出CO保护缺血/缺氧细胞损伤的可能机制，即缺血期CO竞争结合线粒体呼吸复合酶，抑制电子传递，暂时性抑制缺血期线粒体异常的氧化磷酸化功能，减少活性氧，保护呼吸链；再复氧期呼吸链完整的线粒体氧化磷酸化功能相对正常，心肌损伤减轻。本项目采用一氧化碳释放分子-2于缺血/缺氧期干预大鼠和培养的心肌细胞，通过Clark电极、高效液相色谱、激光共聚焦显微镜等方法，分别观察心肌缺血/缺氧期和再灌注/复氧期线粒体结构、氧化磷酸化功能、呼吸复合酶活性，阐明CO保护心肌细胞线粒体呼吸功能的机制，为CO用于临床抢救心跳骤停提供科学依据。

中文关键词： 一氧化碳；心肺复苏；电子传递链；线粒体

英文摘要： Carbon monoxide (CO) exerts anti-inflammatory, antioxidant, anti-apoptosis and multiple protective effects, is an important gaseous molecules. Our previous study confirmed that endogenous CO production induced by Hemin can protected postresuscitation myocardial dysfunction in rats and hypoxia/reoxygenation injury in cultured myocardial cells, and CO significantly protected myocardial mitochondrial integrity and mitochondrial aerobic respiratory function during reoxygenation period. However the mechanism of protective effect of CO is unknown. Since CO can be combined with the mitochondrial respiratory complex enzyme IV, We first proposed the possible mechanism of protective role of CO against ischemic myocardial injury. It is that carbon monoxide can be competitively combined with the mitochondrial respiratory complex enzyme during the period of ischemia, inhibit mitochondrial electron transfer chain, transiently inhibit abnormal mitochondrial oxygen phosphorylation function to reduce reactive oxygen species and to protect the respiratory chain; Mitochondrial respiratory chain having being protected during ischemia phase has relatively normal oxidative phosphorylation function during reperfusion period, myocardial injury is reduced. In this project we use exogenous CO in ischemia / hypoxia phase to intervene cardiopulmonary resuscitation rats model and cultured myocardial cells in vitro, separately observe mitochondrial structure and function of oxidative phosphorylation, respiratory complex enzyme activities in myocardial ischemia /hypoxia phase and reperfusion / reoxygenation phase by the Clark electrode, high performance liquid chromatography, laser confocal microscopy and other methods, to clarify the mechanism of CO protection of mitochondrial respiratory function of the myocardial cells, and to provide a scientific basis for clinical rescue cardiac arrest patients using CO.

英文关键词： carbon monoxide;cardiopulmonary resuscitation;lectron transport chain;mitochondria