乙酰胆碱对离体大鼠缺血/复灌心脏的保护作用及其机制  

Myocardial protective effect of acetylcholine against ischemia/reperfusion injury and its underlying mechanism

作　　者：孙国铨[1] 崔洁[2] 叶治国[2] 钱令波[2] 王会平[2] 夏强[2] 

机构地区：[1]浙江医学高等专科学校生理教研室,杭州310053 [2]浙江大学医学院生理学系,杭州310058

出　　处：《中国应用生理学杂志》2010年第1期23-27,共5页Chinese Journal of Applied Physiology

基　　金：浙江省教育厅基金资助(20071349)

摘　　要：目的:探讨乙酰胆碱(ACh)预处理抗心肌缺血复灌(I/R)损伤作用及其与线粒体渗透性转换孔和/或线粒体ATP敏感性钾通道的关系。方法:采用离体大鼠心脏Langendorff灌流方法进行全心停灌30min,复灌120min复制I/R模型。测定心室力学指标和复灌各时间点冠脉流出液中乳酸脱氢酶(LDH)含量。实验结束测定心肌组织formazan含量的变化。结果:与单纯I/R组相比,ACh(0.1μmol/L,5min)预处理明显提高心肌细胞的formazan含量,降低复灌期间冠脉流出液中LDH含量,明显改善I/R所致的左室发展压、左心室内压最大上升和下降速率、心率与发展压乘积和左室舒张末压力的下降,缓解冠脉流量的减少。线粒体渗透性转换孔开放剂苍术苷(20μmol/L,复灌前给药20min)和线粒体ATP敏感性钾通道抑制剂5-羟基癸酸(100μmol/L,缺血前给药20min)能明显减弱ACh的保护作用。结论:在大鼠离体心脏灌流模型上,ACh预处理具有抗心脏缺血/复灌损伤的作用,这种保护作用可能与其抑制线粒体渗透性转换孔的开放和促进线粒体ATP敏感性钾通道的开放有关。Objective：To determine whether the cardioprotection of acetylcholine（ACh） against ischemia/reperfusion（I/R） injury is related to mitochondrial permeability transition pore（MPTP） and mitochondrial ATP-sensitive potassium channel（mitoKATP）.Methods：Male Sprague-Dawley rats were used for Langendorff isolated heart perfusion.The hearts were subjected to global ischemia for 30 min followed by 120 min of reperfusion and the left ventricular hemodynamic parameters were measured.Formazan,a product of 2,3,5-triphenyl-tetrazolium chloride （TTC）,which is proportional to myocardial viability,was measured at 490 nm,and the level of lactate dehydrogenase （LDH） in the coronary effluent was measured to evaluate the cardiac injury.Results：The pretreatment with ACh（0.1 mol/L,5 min） before I/R markedly increased myocardial formazan content,reduced LDH release,improved the recovery of the left ventficular developed pressure,±dP/dtmax,and rate pressure product （left ventricular developed pressure multiplied by heart rate） and attenuated the decrease of coronary flow during reperfusion.The opener of MPTP,atractyloside （20 μmol/L） or the inhibitor of mitoKATP,5-hydroxydecanoate（100 μmol/L） abolished the beneficial effect of ACh.Conclusion：In the isolated rat heart,ACh protects myocardium against ischemia/reperfusion injury via inhibiting the opening of MPTP and increasing the opening of mitoKATP in heart.

关 键 词：乙酰胆碱 心脏 缺血/复灌损伤 线粒体渗透性转换孔 线粒体ATP敏感性钾通道 

分 类 号：R331.3[医药卫生—人体生理学]