吗啡预处理对心力衰竭大鼠心肌缺血再灌注损伤时程序性坏死的影响  

Effect of morphine preconditioning on necroptosis during myocardial ischemia-reperfusion injury in rats with heart failure

作　　者：潘永露 何淑芳[2] 黄俊 金世云[2] 张野[2] Pan Yonglu;He Shufang;Huang Jun;Jin Shiyun;Zhang Ye(Department of Anesthesiology,First Affiliated Hospital of Anhui Medical University,Hefei 230022,China;Department of Anesthesiology and Perioperative Medicine,Second Affiliated Hospital of Anhui Medical University,Hefei 230601,China)

机构地区：[1]安徽医科大学第一附属医院麻醉科,合肥230022 [2]安徽医科大学第二附属医院麻醉与围术期医学科,合肥230601

出　　处：《中华麻醉学杂志》2019年第8期1005-1008,共4页Chinese Journal of Anesthesiology

基　　金：安徽省科技厅年度重点项目(1301043030);安徽省高校省级自然科学研究重大项目(KJ2014ZD16)。

摘　　要：目的评价吗啡预处理对心力衰竭大鼠心肌缺血再灌注损伤时程序性坏死的影响。方法清洁级健康成年雄性SD大鼠,体重200~230 g,尾静脉注射盐酸多柔比星2 mg/kg,1周1次,连续6周,制备慢性心力衰竭模型,在第8周末将造模成功的30只大鼠采用随机数字表法分为3组(n=10):假手术组(S组)、缺血再灌注组(I/R组)和吗啡预处理组(MPC组)。采用开胸结扎左冠状动脉前降支(LAD)缺血30 min、恢复灌注的方法制备大鼠心肌缺血再灌注损伤模型。S组只缝线,不结扎LAD,其余各组均结扎LAD。MPC组于缺血前股静脉输注吗啡0.1 mg/kg,输注5 min后停止输注5 min,重复3次后进行制备模型。于再灌注120 min时处死大鼠取心脏,采用TTC染色检测梗死区体积(IS)、缺血危险区体积(AAR),计算IS/AAR比值,荧光定量RT-PCR法检测Fas mRNA表达,Western blot法检测Fas、受体相互作用蛋白1(RIP1)和RIP3表达。结果与S组比较,I/R组再灌注120 min时IS和IS/AAR比值增加,Fas及其mRNA、RIP1和RIP3表达上调(P<0.05);与I/R组比较,MPC组再灌注120 min时IS和IS/AAR比值减少,Fas及其mRNA、RIP1和RIP3表达下调(P<0.05)。结论吗啡预处理减轻心力衰竭大鼠心肌缺血再灌注损伤的机制与抑制程序性坏死有关。Objective To evaluate the role of morphine preconditioning on necroptosis during myocardial ischemia-reperfusion(I/R)injury in the rats with heart failure.Methods Clean-grade adult male Sprague-Dawley rats,weighing 200-230 g,were injected with 2 mg/kg doxorubicin via the tail vein once a week for 6 consecutive weeks to establish the chronic heart failure model.Thirty rats with chronic heart failure at the end of 8th week were divided into 3 groups(n=10 each)using a random number table method:sham operation group(group S),I/R group and morphine preconditioning group(group MPC).Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion in each group except group S.In group MPC,the rats were subjected to 3 cycles of 5-min infusion of 0.1 mg/kg morphine via the femoral vein at 5 min intervals before ischemia.The animals were sacrificed at the end of reperfusion,and the myocardial specimens were obtained for determination of the area at risk(AAR),infarct size(IS),expression of Fas mRNA(by quantitative real-time polymerase chain reaction)and expression of Fas,receptor-interacting protein 1(RIP1)and RIP3(by Western blot).The IS/AAR ratio was calculated.Results Compared with group S,the IS and IS/AAR ratio were significantly increased at the end of reperfusion,and the expression of Fas protein and mRNA,RIP1 and RIP3 was up-regulated in group I/R(P<0.05).Compared with group I/R,the IS and IS/AAR ratio were significantly decreased at the end of reperfusion,and the expression of Fas protein and mRNA,RIP1 and RIP3 was down-regulated in group MPC(P<0.05).Conclusion The mechanism by which morphine preconditioning reduces myocardial I/R injury is related to inhibiting necroptosis in the rats with heart failure.

关 键 词：吗啡 缺血预处理 心力衰竭 心肌再灌注损伤 坏死 

分 类 号：R54[医药卫生—心血管疾病]