七氟烷预处理对老年大鼠心肌线粒体敏感性钾通道的影响

Effect of Sevoflurane Preconditioning on Myocardial Mitochondrial Sensitive Potassium Channel in Aged Rats with Ischemic

目的:研究七氟烷预处理对老年大鼠心脏功能和线粒体形态结构的影响及其机制。方法:选取清洁级健康雄性SD大鼠60只,首先建立稳定的离体心脏灌注模型,经KH平衡液平衡15 min后随机将其分为假手术组、缺血再灌注(I/R)组、七氟烷预处理Ⅰ(SevoⅠ)组(0.5 Mac七氟烷)、七氟烷预处理Ⅱ(SevoⅡ)组(1.0 Mac七氟烷)、SevoⅠ+5-HD组、SevoⅡ+5-HD组,每组10只。比较平衡后,缺血前,再灌注5、15、30 min时的冠脉血流量(coronary flow,CF)、心率(heart rate,HR)、左室发展压(left ventricular developed pressure,LVDP)和左室舒张末压(left ventricular end diastolic pressure,LVEDP)。观察灌注末胞浆膜下线粒体(subsarcolemmal mitochondria,SSM)、心肌纤维间线粒体(intermyocardial fiber mitochondria,IFM)的形态学变化。结果:再灌注5、15、30 min,SevoⅠ组与SevoⅡ组CF、HR、LVDP均高于I/R组(P<0.01),LVEDP均低于I/R组(P<0.01);SevoⅠ+5-HD组CF、HR、LVDP均低于SevoⅠ组(P<0.01),LVEDP均高于SevoⅠ组(P<0.01);SevoⅡ+5-HD组CF、HR、LVDP均低于SevoⅡ组(P<0.01),LVEDP均高于SevoⅡ组(P<0.01)。电镜结果显示,SevoⅠ组、SevoⅡ组心肌线粒体形态保存较好,但联合应用K通道抑制剂5-HD后(SevoⅠ+5-HD组、SevoⅡ+5-HD组),其保护效应消失。结论:七氟烷预处理可增加老年大鼠缺血心脏的CF,减轻缺血再灌注对心肌细胞线粒体的损伤,而K通道抑制剂5-HD可以取消七氟烷预处理对老年大鼠缺血心肌的保护作用。

Objective:To study the effects of Sevoflurane preconditioning on cardiac function and mitochondrial morphology in aged rats with ischemia and its mechanism.Method:A total of 60 healthy male SD rats of clean grade were selected.First,establish a stable isolated heart perfusion model,after equilibrium of KH equilibrium liquid equilibrium 15 min,they were randomly divided into sham operation group,ischemia reperfusion group(I/R),sevoflurane preconditioningⅠ(SevoⅠ)group(0.5 Mac Sevoflurane),Sevoflurane preconditioningⅡ(SevoⅡ)group(1.0 Mac Sevoflurane),SevoⅠ+5-HD group,SevoⅡ+5-HD group,10 rats in each group.The coronary flow(CF),heart rate(HR),left ventricular developed pressure(LVDP)and left ventricular end diastolic pressure(LVEDP)after the balance,before ischemia,reperfusion 5,15 and 30 min were compared.The morphological changes of subsarcolemmal mitochondria(SSM)and intermyocardial fiber mitochondria(IFM)at the end of perfusion were observed.Result:Reperfusion 5,15 and 30 min,the CF,HR and LVDP in SevoⅠgroup and SevoⅡgroup were higher than those of I/R group(P<0.01),LVEDP were lower than those of I/R group(P<0.01).The CF,HR and LVDP in SevoⅠ+5-HD group were all lower than those of SevoⅡgroup(P<0.01).Electron microscopy showed that myocardial mitochondria were well preserved in SevoⅠgroup and SevoⅡgroup,but the protective effect disappeared after combined application of K channel inhibitor 5-HD(SevoⅠ+5-HD group,SevoⅡ+5-HD group).Conclusion:Sevoflurane preconditioning can increase the CF of ischemic heart in aged rats,alleviate the injury of mitochondria after myocardial ischemia and reperfusion,and K-channel inhibitor 5-HD can cancel the protective effect of sevoflurane preconditioning on ischemic myocardium in aged rats.