吗啡预处理对心肌缺血再灌注损伤大鼠延迟性心肌保护的作用机制研究

Involvements of Heme Oxygenase-1 and MitOKATe Channel in Delayed Preconditioning Elicited by Morphine in Rat Hearts

【目的】研究血红素氧合酶-1（HO-1）和线粒体ATP敏感性钾（Mitochondrial KATP，mitoKATP）通道与吗啡预处理的延迟性心肌保护作用的关系。【方法】雄性Wistar大鼠随机分为5组。IR组（A组），腹腔注射生理盐水5mL，24h后行心肌缺血再灌注（IR）；Mor组（B组），腹腔注射吗啡3mg／kg（用生理盐水稀释至5mL），24h后行心肌IR；HO-1阻滞剂（ZnPP—IX）＋Mor组（C组），腹腔注射ZnPP—IX 20μg／kg，30min后腹腔注射吗啡3mg／kg，24h后行心肌IR；mitoKATP通道阻滞剂（5-HD）＋Mor组（D组），腹腔注射5-HD5mg／kg，20min后腹腔注射吗啡3mg／kg，24h后行心肌IR；Mor＋5-HD组（E组），腹腔注射吗啡3mg／kg，24h后行IR，但在缺血前10min腹腔注射5-HD5mg／kg。各组于缺血前、缺血25min、再灌注30、60、120min记录大鼠心率（HR）、平均动脉压（MAP）。心肌缺血再灌注结束即刻采用EB／TTC双重染色，称重法测定心肌梗死面积，比较各组心肌梗死面积发生情况。【结果】和A组相比，B组心肌梗死面积明显减小，且差异有显著性（P〈0．05）；C组、D组和E组心肌梗死面积无明显差异（P〉0．05）。【结论】HO-1和mitoKATP通道参与了吗啡预处理的延迟性心肌保护作用；mitoKATP通道既是启动因子又是效应器。

[Objective] To explore whether heine oxygenase-1 （HO-1） and mitochondrial ATP sensitive potassium （mitOKATe） channel are involved in morphine-induced delayed cardioprotection. [Methods] Wistar rats were randomly divided into 5 groups. And 25 rain regional ischemia plus 2 h reperfusion （IR） at 24 h post treatment of 0.9% sodium chloride 5 mL in group IR; morphine 3mg/kg in group Mor; HO-linhibitor ZnPP-IX 20μg/kg plus morphine 3 mg/kg in group ZnPP4-Mor; mitOKATe channel antagonist 5-hydroxydecanoic acid （5-HD） 5 mg/kg plus morphine 3 mg/kg in group 5-HD＋Mor. In group Mor＋5-HD, IR 24 h after morphine 3mg/kg and 10 rain after 5-HD 5 mg/kg. Heart rate （HR） and mean arterial blood pressure （MAP） were recorded at pre-ischemia, 30, 60, 120 rain post-reperfusion. Infarct size （percentage area at risk） was assessed at the end of reperfusion. [Results] No statistical differences in HR or MAP existed among five groups. Infarct size was 60.0% ± 10.5 % in group IR. Pretreatment with morphine reduced infarct size to 27.4%±8.2% after 24 h in group Mor. The reduction of infarct size by morphine was abolished by 5-HD given either before morphine application or before ischemia. And cardioprotection was abolished by ZnPP-IX given before morphine in group ZnPP＋Mor . [Conclusion] Both HO-1 and mitoKATP are probably involved in delayed cardioprotection evoked by morphine. And mitOKATp channel may serve as both a trigger and a effeetor in cardioproteetion.