20-HETE在心肌缺血再灌注损伤中的作用及机制研究  

The effect and mechanisms of 20-HETE on myocardial ischemia reperfusion injury

作　　者：韩勇[1] 郭立荣[2] 孔德营[1] 蒋慧[1] 田虹[1] 

机构地区：[1]遵义医学院生理学教研室,贵州遵义563000 [2]遵义医学院形态学实验室,贵州遵义563000

出　　处：《重庆医学》2015年第32期4465-4468,共4页Chongqing medicine

基　　金：国家自然科学基金项目(81460040);贵州省科学技术基金项目(黔科合LH字[2014]7544号)

摘　　要：目的探讨20-羟二十烷花生四烯酸(20-HETE)在离体心肌缺血再灌注损伤中的影响及机制。方法大鼠离体心脏通过Langendorff装置建立缺血再灌注模型,心脏缺血35min再灌注40min。缺血前10min开始分别灌流HET0016(1μmol/L)及不同浓度的20-HETE(10、30、50nmol/L),直至整个缺血再灌注结束。通过Powerlab/8P系统实时记录离体心脏血流动力学指标;心肌梗死面积采用TTC染色法测定;活性氧簇(ROS)及蛋白质羰基化水平分别使用DHE荧光探针法和DNPH法检测。结果灌流液中使用HET0016显著改善了缺血诱导的心肌收缩力的下降,抑制20-HETE的生成后,减少了心肌梗死面积的发生(P<0.05);而灌流液中外源性加入20-HETE后加重了心肌再灌注后损伤(P<0.05)。同时,HET0016明显降低了再灌注后ROS的生成及蛋白质过氧化,而加入20-HETE后显著促进了ROS生成和蛋白质过氧化(P<0.05)。结论 20-HETE通过增加ROS生成导致蛋白质过氧化加重心肌缺血再灌注损伤。Objective To investigate the effect of 20-HETE on the isolated myocardial ischemia reperfusion injury and to explore its underlying mechanisms.Methods Experiments were performed in isolated rat hearts subjected to 35 min of ischemia followed by 40 min of reperfusion in Langendorff preparations.HET0016（1μmol/L）and various concentrations（10,30 or 50nmol/L）of 20-HETE were infused 10 min before the onset of ischemia and throughout the reperfusion period.Cardiac hemodynamic changes and myocardial contractility were continuously recorded with the Powerlab/8Psystem.Myocardial infarct size was measured by TTC staining.The level of ROS and the protein carbonyl content were determined by DHE fuorescence and DNPH method,respectively.Results Perfusion with HET0016 significantly improved myocardial ischemia reperfusion injury reduction in cardiac contractility,after inhibited the production of 20-HETE significantly reduced the occurrence of myocardial infarction area（P〈0.05）,but exogenous join 20-HETE aggravated I/R-induced myocardial injury（P〈0.05）.Myocardial ischemia reperfusion injury significantly increased production of ROS and oxidative stress,both of which were significantly inhibited by HET0016 and enhanced by 20-HETE administration（P〈0.05）.Conclusion 20-HETE stimulates ROS production and enhance protein carbonylation,which aggravates myocardial ischemia reperfusion injury.

关 键 词：花生四烯酸类 再灌注损伤 活性氧 蛋白质羰基化 

分 类 号：R542.2[医药卫生—心血管疾病]