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阿片受体在缺血预处理中的作用

The effect of opioid receptors on ischemic preconditioning

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【作者】 王欣李玉光张元春袁忠祥

【Author】 WANG Xin, LI Yuguang, ZHANG Yuanchun, et al. Center of Cardiology, First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China.

【机构】 汕头大学医学院第一附属医院

【摘要】 目的 研究阿片受体激动在缺血预处理限制心肌梗死 (心梗 )范围作用中的地位。方法 建立在体家兔心脏缺血再灌注模型 ,观察阿片受体拮抗剂纳洛酮对缺血预处理心肌保护作用的影响。在离体兔心模型上 ,观察阿片受体激动剂吗啡代替短暂缺血刺激 ,对随后发生的急性心梗范围的影响 ,并用纳洛酮及蛋白激酶C阻断剂Chelerythrine分别进行干预。电镜观察吗啡预处理对离体心脏缺血心肌超微结构改变的影响。结果 在体心脏模型上 ,5min缺血及 10min再灌注的预处理可显著缩小随后30min缺血引起的心梗范围 (P <0 0 1) ;在预处理前 10min或 30min、缺血前 5min给予纳洛酮均可使预处理所产生的限制心梗范围的作用消失。离体心脏经历 5min全心缺血及 10min再灌注的预处理后 ,可缩小心梗范围 (P <0 0 5 ) ;在缺血前如给予吗啡预灌注 15min ,亦可缩小心梗范围 (P <0 0 5 ) ,其作用可被纳络酮或Chelerythrine分别阻断。 30min缺血后心肌线粒体等超微结构严重受损 ,如给吗啡预灌流 ,心肌损伤明显减轻。结论 阿片受体激动参与了缺血预处理的心肌保护 ;吗啡预处理可以减轻缺血心肌损伤及产生限制心梗范围的心肌保护作用 ;吗啡是通过心脏局部的阿片受体介导 ,激活蛋白激酶C从而产生心肌保护作用

【Abstract】 Objective: To investigate the role of opioid receptors in the infract limiting effect of ischemic preconditioning in rabbit hearts. Methods: In the in vivo rabbit heart model, the effect of naloxone, an opioid antagonist, on the cardioprotection afforded by ischemic preconditioning was observed. In the in vitro rabbit heart model, the effect of mophine pretreatment on the infarct size of acute myocardial infarction and changes of the ultrastructure of ischemic myocardium were observed. Results: In the in vivo heart model, naloxone could completely abolished the protection afforded by ischemic preconditioning when given either 10 minutes before brief preconditioning ischemia or 5 minutes before 30 minutes ischemia. In the in vitro heart model, preconditioning with 5 minutes global ischemia followed by 10 minutes reperfusion could reduce infarct size (P<0 05). Morphine could also reduce infarct size (P<0 05) when perfused for 15 minutes before 30 minutes ischemia. Naloxone, or chelerythrine, a selective protein kinase C inhibition, can abolish the morphine induced cardioprotection. After 30 minutes global ischemia, electron microscopic myocardial damage in morphine group was less severe than in control group. Conclusions: (1) Opioid receptors may be involved in ischemic preconditioning in rabbit hearts. (2) Morphine pretreatment can reduce ischemic myocardium ultrastructure damage and limit infarct size. (3) Mophine induced cardioprotection is mediated via local myocardial opioid receptors and protein kinase C.

  • 【文献出处】 中华胸心血管外科杂志 ,Chinese Journal of Thoracic and Cardiovaescular Surgery , 编辑部邮箱 ,2001年02期
  • 【分类号】R541
  • 【被引频次】23
  • 【下载频次】146
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