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线粒体Slo_1通道激活引起的心肌保护作用涉及线粒体渗透性转换机制 被引量：2

Cardioprotection of mitoSlo_1 channel activation involves mitochondrial permeability transition in ischemia and reperfusion of rat hearts
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摘要 目的:研究线粒体大电导钙激活钾通道(mitoSlo1通道)开放是否具有心肌保护作用及其是否与抑制线粒体渗透性转换孔的开放有关。方法:采用离体大鼠心脏灌流方法,结扎冠状动脉左前降支30min和复灌120min复制局部缺血/复灌损伤模型,测定心肌梗死面积、冠脉流出液中乳酸脱氢酶(LDH)含量及各项心室力学指标。提取大鼠心肌线粒体,分光光度法测定钙诱导下520nm吸光度的改变。结果:与单纯缺血/复灌组相比,Slo1通道激动剂NS1619预处理组明显降低离体心脏缺血/复灌后的梗死面积[(17.21±5.59vs46.54±3.60)%]和复灌期冠脉流出液中LDH含量[(69.21±8.30vs253.79±15.85)U/L],促进左室动力学的恢复;线粒体渗透转换孔开放剂a-tractyloside拮抗了NS1619的作用。在分离的心脏线粒体,NS1619预处理组520nm处吸光度的下降明显低于单纯加钙组[(10.70±3.22vs21.53±2.57)%]。结论:mitoSlo1通道激活具有抗心肌缺血/复灌损伤的保护作用,其机制可能与抑制线粒体渗透转换孔开放有关。 Objective： To investigate whether the cardioprotection of mitochondrial Slol channel （mitoSlo1 channel） is associated with mitochondrial permeability transition in isolated rat hearts subjected to ischemia and reperfusion. Methods： Isolated perfused rat hearts were suhiected to 30 rain regional ischemia （occlusion of left anterior descending artery） and 120 rain reperfusion. The infarct size,lactate dehydrogenase （LDH） release during reperfusion and ventricular hemodynamic parameters were measured. Results： Pretreatment with mitoSlol channel opener,NS1619 10μmol/L for 10min reduced the infarct size and LDH release,and improved the recovery of left ventricular developed pressure, left ventricular end-diastolic pressure, maximal rise/fall rate of left ventricular pressure and coronary flow during reperfusion. Administration of atractyloside （20μmol/L）, an opener of mitochondrial permeability transition pore,for 20 rain （last 5 rain of ischemia and first 15 rain of reperfusion） attenuated the reduction of infarct size and LDH release and improvement of left ventricular performance induced by NS1619. In the isolated mitochondria, a significant inhibition of Ca^2＋ -induced swelling was observed when mitochondria were incubated with NS1619. Conclusion： MitoSlo1 channel activation by NS1619 protects the myocardium against ischemia and reperfusion injury by inhibiting mitochondrial permeability transition pore opening.
作者 叶挺梅 叶治国 高琴 夏强
机构地区 浙江大学医学院生理学教研室
出处 《浙江大学学报（医学版）》 CAS CSCD 2005年第5期441-446,共6页 Journal of Zhejiang University(Medical Sciences)
关键词 线粒体 心肌/病理学 心肌再灌注损伤 局部缺血 钙 钾通道/生理学 Mitochondria Myocardium/pathol Myocardial reperfusion injury lischemia ~ Calcium Potassium channels/physiol
分类号 R541 [医药卫生—心血管疾病]
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参考文献11

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同被引文献26

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  • 3Olanrewaju HA,Gafurov BS,Lieberman EM.Involvement of K+ channels in adenosine A2A and A2B receptor-mediated hyperpolarization of porcine coronary artery endothelial cells[J].J Cardiovasc Pharmacol,2002,40(1):43-49.
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浙江大学学报（医学版）
2005年 第5期

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