一氧化氮在吗啡后处理对心肌缺血再灌注损伤保护中的作用  

Nitric Oxide Mediates Cardioprotective Effects of Morphine Postconditioning in Myocardial Ischemia-reperfusion

作　　者：王志[1] 赵惠娟[2] 金冬梅[3] 车月娟[1] 李玉娟[1] 王飞[1] 彭书崚[1] 

机构地区：[1]中山大学附属第二医院麻醉科,广东广州510120 [2]中山大学附属第一医院手术室,广东广州510120 [3]中山大学附属第二医院康复科,广东广州510120

出　　处：《中山大学学报（医学科学版）》2010年第5期641-645,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省医学科研基金(A2008179)

摘　　要：【目的】探讨吗啡后处理对急性心肌缺血/再灌注损伤的保护作用以及对信号通路eNOS/NO的影响。【方法】SD大鼠56只随机分成4组,每组14只:S组(假手术,只穿线,不结扎),I/R组(单纯缺血再灌注),M组(吗啡后处理+缺血再灌注),L+M组(L-NAME+吗啡后处理+缺血再灌注)。除S组外,所有大鼠心脏都经历45min缺血和120min再灌注。观察血流动力学指标,于再灌注120min时,各组随机取9只大鼠,用TTC法染色,计算心肌缺血梗死区(IA/AR);其余5只大鼠,取心肌,用Western Blot技术分析总eNOS和磷酸化eNOS的蛋白表达,硝酸盐还原酶法测定心肌NO含量。运用SPSS12.0统计软件,统计学分析采用方差分析及SNK检验。【结果】与I/R组比较,M组梗死面积明显缩小,(32±2.8)%vs(49±2.9)%(P<0.01);磷酸化eNOS的蛋白表达明显增加;心肌组织内NO含量也明显增加。非选择性一氧化氮合成酶抑制剂,l-NAME完全消除吗啡后处理对心肌的保护作用,明显降低吗啡后处理所诱导的心肌组织内NO含量的增加,但并没有抑制吗啡后处理所诱导的磷酸化eNOS蛋白表达的增加。【结论】大鼠在体心脏缺血模型,吗啡后处理可通过eNOS/NO信号通路,抗心肌缺血/再灌注损伤。Objective To investigate the cardioprotective effect of morphine postconditioning on ischemic reperfused rat heart and to test the hypothesis that phosphorylation of eNOS by morphine may participate in the cardioprotective effect of morphine after myocardial ischemia and reperfusion.Methods Rats subjected to 45 min of myocardial ischemia followed by 120 min of reperfusion were assigned to the following groups：sham-operated（S group）,ischemia-reperfusion（I/R group）,morphine postconditioning ＋ I/R（M group）,morphine postconditioning ＋ l-NAME ＋ I/R（L ＋ M group）.Infarct size was assessed by triphenyltetrazolium chloride staining.Akt phosphorylation expression was assessed by immunoblotting.The nitric oxide concentrations in cardiac tissue were quantified by a chemiluminescence detector.Statistical analysis was performed using SPSS 12.0 for Windows software.The statistical significance was determined by analysis of variance followed by the Student-NewmanKeuls test.Results Morphine postconditioning reduced infarct size compared with that in the I/R group：32 ± 2.8 % versus 49 ± 2.9 %（P0.01）.eNOS phosphorylation expression increased after morphine postconditioning.Morphine postconditioning also resulted in marked increase in NO content.The cardioprotective effects and increased NO production of morphine postconditioning were significantly inhibited by L-NAME.However,pretreatment with L-NAME could not inhibit the phosphorylation of eNOS in morphine-treated rats.Conclusion Morphine postconditioning can reduce ischemia-reperfusion injuries in rat heart by increasing the phosphorylation of eNOS and the NO production.

关 键 词：心肌再灌注损伤 后处理 吗啡 一氧化氮 

分 类 号：R543.31[医药卫生—心血管疾病]