吗啡后处理抑制缺血再灌注损伤大鼠心肌细胞凋亡及其抗氧化机制  

Anti-apoptotic Effect of Morphine Postconditioning on Myocardial Ischemia-Reperfusion Injury and Its Anti-oxidative Stress Mechanism

作　　者：王志[1] 赵惠娟[2] 彭俊[1] 车月娟[1] 李玉娟[1] 曾静贤[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510080

出　　处：《中山大学学报（医学科学版）》2009年第5期532-536,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】探讨吗啡后处理抑制缺血再灌注损伤大鼠心肌细胞凋亡的作用以及与氧化应激的关系。【方法】SD大鼠45只随机分成3组,每组15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)。再灌注末,TUNEL染色检测细胞凋亡,检测氧化应激指标和心肌caspase-3的活性。【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(18.0±1.1)%,吗啡后处理显著降低心肌细胞凋亡指数(10.8±1.2)%,P<0.01)。与I/R组相比,吗啡后处理明显上升了心肌组织超氧化物歧化酶(SOD)活力,降低了心肌组织丙二醛(MDA)含量(P<0.01)。与假手术的对照组比较,缺血再灌注损伤组caspase-3活性明显增强(P<0.01),而吗啡后处理组明显降低了缺血再灌注损伤所增强的caspase-3活性(P<0.01)。【结论】大鼠在体心脏缺血模型,吗啡后处理可通过抗氧化应激,抑制缺血再灌注损伤诱导的心肌细胞凋亡。【Objective】 To investigate the anti-apoptotic effect of morphine postconditioning on myocardial ischemia-reperfusion injury and its relationship to the oxidative stress. 【Methods】 Forty-five rats were randomly separated into 3 groups： sham-operated （S group）, ischemia-reperfusion （I / R group）, morphine postconditioning ＋ I / R （M group）. Cardiac myocyte apoptosis was determined quantitatively by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） methods. The amount of malondialdehyde （MDA） and the activity of superoxide dismutase （SOD） and caspase-3 in myocardium were measured at the end of the reperfusion period. 【Results】 A significant number of TUNEL positive cells [（18.0 ± 1.1）%] were observed in myocardial tissue from hearts subjected to 45 min of myocardial ischemia followed by 120 min of reperfusion. Administration of morphine exerted a significant anti-apoptotic effect, as evidenced by reduced TUNEL-positive staining [（10.8 ± 1.2）%, P〈0.01 versus I / R]. Compared with the I / R group, treatment with morphine inhibited the rise in MDA and increased SOD activity in the myocardial tissue （P〈0.01）. Caspase-3 activity was increased in the myocardial tissue after ischemia-reperfusion injury compared with that in sham-operation group （P〈0.01）. Treatment with morphine reduced this elevation compared with the I / R group （P〈0.01）. 【Conclusion】 Morphine postconditioning can significantly reduce ischemia / reperfusion-induced cardiomyocyte apoptosis via mediating oxidative stress in rats.

关 键 词：心肌再灌注损伤 后处理 吗啡 超氧化物歧化酶 丙二醛 凋亡 

分 类 号：R543.31[医药卫生—心血管疾病]