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吗啡后处理抗心肌缺血再灌注损伤心肌细胞凋亡中的作用及机制 被引量：2

PI3K/AKT mediates the antiapoptotic effect mechanism of morphine postconditioning on myocardial ischemia-reperfusion
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摘要 目的探讨吗啡后处理抑制心肌缺血/再灌注损伤大鼠心肌细胞凋亡的作用以及对信号通路PI3K/AKT的影响。方法采用麻醉开胸大鼠在体心脏缺血模型,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,再灌注前3min和再灌注后2min内静脉注入吗啡1.25mg/kg),W+M组(wortmannin+吗啡后处理+缺血再灌注,左冠状动脉前降支结扎前20min静脉注入15ug/kgwortmannin,特异性的PI3K阻断剂)。除S组外,所有大鼠心脏都经历45min缺血和120min再灌注。再灌注120min时,各组随机取9只大鼠,TUNEL染色检测心肌细胞凋亡。其余5只大鼠采用WesternBlot法测定心肌组织总AKT和磷酸化AKT的表达水平。结果再灌注120min,可在I/R组缺血区心肌检测到大量凋亡心肌细胞18±1.14%,吗啡后处理显著降低心肌细胞凋亡指数(10.8±1.24%,P<0.01);吗啡后处理使磷酸化AKT的蛋白表达明显增加。特异性的PI3K阻断剂,wortmannin完全消除了吗啡后处理抑制缺血/再灌注损伤大鼠心肌细胞凋亡的作用,及抑制磷酸化AKT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PI3K/AKT信号通路,抑制心肌缺血/再灌注损伤心肌细胞凋亡。 Objective To investigate the anti-apoptotic effect of morphine postconditioning on myocardial ischemia-reperfusion and its relationship to the PI3K/AKT signaling pathway. Methods Rats subjected to 45 min of myocardial ischemia followed by 120 rain 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 ＋ wortmannin（a specific PI3K inhibitor） ＋I/R（W＋M group）.Cardiae myocyte apoptosis was determined quantitatively by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） methods. Akt phosphorylation expression was assessed by immunoblotting. Results A significant number of TUNEL positive cells （18＋1.14%） were observed in myocardial tissue from hearts subjected to ischemia and reperfusion. Administration of morphine exerted a significant antiapoptotic effect, as evidenced by reduced TUNEL-positive staining （10.8 ±1.24,P〈0.01 versus I/R）. Akt phosphorylation expression was increased after morphine postconditioning. These effects of morphine postconditioning were significantly inhibited by wortmannin. Conclusion In vivo, morphine postconditioning can significantly reduce ischemia-reperfusion injuryinduced myocardial apoptosis,partly by mediating the activation of the PI3K pathway and phosphorylation of Akt.
作者 王志 王飞 金冬梅 纪风涛 李玉娟 曾静贤
机构地区 中山大学附属第二医院麻醉科 中山大学附属第二医院康复科
出处 《岭南现代临床外科》 2009年第4期311-313,共3页 Lingnan Modern Clinics in Surgery
基金 广东省医学科研基金(A2008179)
关键词 心肌再灌注损伤 后处理 吗啡 凋亡 蛋白质丝氨酸苏氨酸激酶 Myocardial repcrfusion injury Postconditioning Morphine Apoptosis Akt
分类号 R614 [医药卫生—麻醉学]
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共引文献26

同被引文献44

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岭南现代临床外科
2009年 第4期

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