摘要
目的:探讨δ-阿片受体是否参与缺血后处理对抗心肌缺血/复灌(I/R)损伤和心肌细胞低氧/复氧(H/R)损伤作用及其机制。方法:采用离体大鼠心脏Langendorff灌流模型,全心停灌30 min、复灌120 min复制I/R模型。测定心室力学指标和复灌时冠脉流出液中乳酸脱氢酶(lactate dehydrogenase,LDH)活性,实验结束测定心肌组织formazan含量。酶解分离的心肌细胞采用低氧60min、复氧60min复制H/R模型,测定心肌细胞存活率。结果:在离体心脏模型上,与I/R组相比,缺血后处理组(停灌后复灌即刻立即给予6次全心停灌/复灌循环)心肌组织的formazan含量明显增高,复灌期间冠脉流出液中LDH明显降低,同时缺血后处理明显改善心室力学指标,缓解冠脉流量的减少;在分离心肌细胞模型上,低氧后处理明显提高心肌细胞存活率。δ-阿片受体阻断剂naltrindole(NTI)和线粒体钙激活钾通道(KCa)阻断剂paxilline(Pax)在离体大鼠心脏模型和分离心肌细胞模型上均能明显减弱缺血后处理的作用。在心肌细胞模型上,与H/R组相比,δ-阿片受体激动剂DADLE明显提高心肌细胞存活率,其作用可被paxilline所阻断。结论:缺血后处理具有抗心肌缺血/复灌损伤的作用,这种保护作用可能与其激活δ-阿片受体和开放KCa有关。
Aim： To investigate the effect of δ-opioid receptors in the cardioprotection elicited by ischemic postconditioning and the underlying mechanism. Methods： The isolated perfused hearts of male Sprague-Dawley rats were subjected to 30 min of global ischemia followed by 120 min of reperfusion. Formazan content of myocardium was measured spectrophotometrically, and the activity of lactate dehydrogenase （LDH） in the coronary effluent was measured. In isolated ventricular myocytes hypoxic postconditioning was achieved by 3 cycles of 5 min reoxygenation/5 min hypoxia starting at the beginning of reoxygenation, and cell viability was measured.Results： In the Langendorff perfused rat heart modal, ischemic postconditioning （6 cycles of 10 s reperfusion/10 s global ischemia starting at the beginning of reperfusion） increased formazan content, reduced LDH release, improved the recovery of the left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure and rate pressure product （left ventricular developed pressure multiplied by heart rate）, attenuated the decrease of coronary flow during reperfusion and increased the isolated cell viability. Pretreatment with naltrindole, an antagonist of δ-opioid receptors and calcium-activated potassium channel （KCa） blocker paxilline attenuated the effect of ischemic/hypoxic postconditioning.Conchtsion： The findings indicate that ischemic postconditioning protects myocardium against ischemia/reperfusion injury via activating δ-opioid receptors and opening KCa.
出处
《中国应用生理学杂志》
CAS
CSCD
北大核心
2008年第2期184-189,共6页
Chinese Journal of Applied Physiology
基金
浙江省教育厅资助项目(20061016)
关键词
心脏
缺血后处理
阿片受体
钙激活钾通道
heart
ischemic postconditioning
opioid receptor
calcium-activated potassium channel
