瑞芬太尼预处理对缺血再灌注心肌线粒体功能的影响及机制

目的观察瑞芬太尼预处理对大鼠离体心脏缺血再灌注时心肌线粒体功能的影响，并探讨其机制。方法成年雄性SD大鼠36只，随机分为I／R组、RPC组、5HD＋RPC组，各12只。建立Langendorfff离体心脏灌注模型，用K－H液平衡20min。I／R组缺血前用K-H灌注液灌注45min；RPC组缺血前用含瑞芬太尼的灌注液灌注5min，再用K—H液冲洗5min，共3次；5HD＋RPC组用含有5-HD线粒体KATP通道阻断剂与瑞芬太尼的混合液灌注，共计45min。缺血30min和再灌注60min时测定各组心肌梗死面积、线粒体酶活性及线粒体膜电位（MMP）。结果与I／R组比较，RPC组再灌注60min时，梗死面积减少（P〈0．05），而5-HD＋RPC组和I／R组相比差异无统计学意义。与K-H液平衡末比较，各组再灌注60min心肌线粒体酶活性及MMP降低（P〈0．01）。再灌注60min后，RPC组上述指标高于I／R组（P〈0．05）。结论瑞芬太尼预处理明显改善大鼠离体心脏缺血再灌注时心肌线粒体功能，其机制与开放线粒体ATP敏感性钾通道有关。

Effect of remifentanil preconditioning on mitochondria function following ischemia-reperfusion in isolated rat hearts

Objective To investigate the effects of remifentanil preconditioning on myocardial following ischemiareperfusion（I/R） in isolated rat hearts. Methods 36 adult male SD rats were randomly divided into 3 groups （n = 12 each） ：I/R group,RPC group and 5-HD ＋ RPC group. The animals were anesthetized with intraperitaneal pentobarbital 30 mg/kg and heparinized. After a 20min stabilization period , I/R group recived 45 min reperfusion before isehemia, PRC group recived 3 episodes of 5min remifentanil perfusion before isehemia. 5-HD ＋ RPC group recived 5-HD（ a selective mitochondrial mitoKATP channel blocker） ,which started 10min before PRC. All the hearts were subjected to 30 ischemia followed by 60 rain reperfusion. The size of myocardial infract were measured at the end of reperfution （T2）and the enzyme activities and mitochondrial membrane potential（MMP） were also measured at the end of post-preparation equilibration（T1 ） and T2. Results PRC significantly decreased the size of myocardial infract as compareed with I/R group , while there was no significantly difference between the I/R and 5-HD ＋ RPC group. Mitochondrial enzyme activities （ NADH oxidase, succinate oxidase and cytochrome C oxidase ） and MMP significantly decreased at T2 as compared to the baseline values at T1 in all 3 groups（P 〈0.01 ） and the mitochundrial function in PRC group was the best （P 〈 0.05 or 0.01 ）. Conclusion Remifentanil can significantly improve mitochondtial function at the end of reperfusion. The opening of mitochondrial ATP sensitive K ^＋ channel is involved in the mechanism of the protective effect of remifintanil against I/R injury.