机构地区:[1]上海中医药大学附属龙华医院科研实验中心,上海200032
出 处:《上海中医药杂志》2009年第3期58-62,共5页Shanghai Journal of Traditional Chinese Medicine
基 金:上海市教委重点项目(07ZZ56);国家教育部科学技术研究重点项目(208042)
摘 要:目的观察中药复方冠心康对豚鼠模拟缺血再灌注损伤心室乳头肌细胞电生理作用,初步探讨其心肌保护机制。方法将32只豚鼠随机分为模型组、格列苯脲组、吡那地尔组、冠心康组(每组8只),分离左心室乳头肌标本。模型组于正常台氏液平衡灌流30min后,用模拟缺血缺氧液灌流15min,再用正常台氏液复灌30min。吡那地尔组(100μmol/L)和格列苯脲组(100μmol/L)缺血前行药物预处理,其余步骤同模型组。冠心康组动物预先灌胃给予冠心康溶液生药6g.kg-1.d-1,每日1次,连续14日,然后分离左心室乳头肌,其余步骤同模型组。采用细胞内标准玻璃微电极技术记录各组动物心室乳头肌细胞电生理参数的变化。结果冠心康预处理对平衡期心肌无明显影响;进一步缩短了缺血早期5min和再灌注早期1min心肌90%动作电位时程(action potential duration at90%repolarization,APD90),与模型组比较有明显差异(P<0.05);自再灌注5min起,冠心康组心肌动作电位时程(action potential duration,APD)迅速恢复,至再灌注30min时50%动作电位时程(action potential duration at50%repo-larization,APD50)和APD90明显长于平衡期(P<0.05);冠心康对各时期心肌静息电位(resting potential,RP)、动作电位振幅(ac-tion potential amplitude,APA)均无明显影响。吡那地尔明显缩短缺血5min、再灌注1min、5min和10min心肌APD50和APD90,与模型组比较有显著差异(P<0.05),而格列苯脲则明显延长缺血和再灌注心肌APD。结论中药复方冠心康对缺血再灌注心肌细胞具有一定的保护作用,其电生理作用可能与影响KATP通道(ATP-sensitive potassium channels,KATP channels)和Ca2+通道有关。Objective To investigate the effects and mechanisms of "Guanxinkang Decoction" on electrophysiological characteristics in isolated papillary muscles of ischemia-reperfusion guinea pig. Methods Thirty-two healthy guinea pigs were randomly divided into model group, herb group, pinacidil group and glibenclamide group; and the ventricular papillary, muscles were isolated quickly. In model group, preparations were superfused with Tyrode' s solution for 30 min, then exposed to 15 min of ischemic conditions, and followed by repeffusion of Tyrode' s solution for 30 min. In pinacidil and glibenclamide group, tissues exposed to 100 μmol/ L pinacidil and glibenclamide for 5 rain before ischemia. In herb group, the guinea pigs were treated with "Guanxinkang Decoction" by 6 g· kg^-1· d^-1 fur 14 d, and then the papillary muscles were isolated. Standard microelectrode technique was used to record and analyze the changes of cellular electrophysiological parameter in guinea-pig papillary muscles during normal perfusion, simulated ischemia, and reperfusion. Results "Guanxinkang Decoction" pretreatment showed no influence on action potential duration(APD) during equilibrium, but it increased ischemia-induced abbreviation of APD during ischemia and early reperfusion. At 5 min of ischemia and 1 min of reperfusion, the action potential duration at 90% repolarization(APD90) in herb group was significantly lower than model group( P 〈0.05 ). In contrast, "Guanxinkang Decoction" pretreatment greatly prolonged APD during later reperfusion. At 30 min of reperfusion, APD50 and APD90 in herb group were significantly higher than equilibrium (P 〈 0.05 ). Pinacidil (ATP-sensitive K channels opener) pretreatment significantly shorted APD50 and APD90 during ischemia and reperfusion compared with model group(P 〈0.05 ). Glibenclamide( ATP-sensitive K channels blocker) pretreatment significantly prolonged APD50 and APD90 during ischemia and reperfusion. Additionally, all drugs had no effect o
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