葛根素对离体大鼠缺血/复灌心脏的保护作用及其作用机制  

THE PROTECTIVE ROLE AND THE MECHANISMS OF PUERARIN ON ISOLATED RAT HEART DURING ISCHEMIA/REPERFUSION

作　　者：潘红阳[1] 高琴[1] 姚慧[2] 夏强[1] 

机构地区：[1]浙江大学医学院生理教研室,浙江杭州310031 [2]杭州师范学院医学院,浙江杭州310012

出　　处：《中国应用生理学杂志》2006年第4期455-459,共5页Chinese Journal of Applied Physiology

基　　金：国家基础科学人才培养基金资助(J0530183);浙江省科技厅基金资助项目(2005C30026)

摘　　要：目的:探讨葛根素(puerarin,Pue)预处理抗心肌缺血/复灌(ischemia/reperfusion,I/R)损伤是否与线粒体渗透性转换孔和/或线粒体ATP敏感性钾通道有关。方法:采用离体大鼠心脏Langendorff灌流方法,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量的变化。结果:与单纯I/R组相比,Pue(0.24mmol/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,明显促进左室发展压、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恢复,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Pue的保护作用。结论:在大鼠离体心脏灌流模型上,Pue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。To determine whether the cardioprotection of puerarin （Pue） against ischemia/reperfusion （I/R） is mediated by mitochondrial transmembrane pore or channels. Methods： Male Sprague-Dawley rats were used for Langendorff isolated heart perfusion. The hearts subjected to global ischemia for 30 min followed by 120 min of reperfusion. Formazan, a product of 2,3,5-triphenyltetrazolium 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 Pue at 0.24 mmol/L for 5 min before ischemia increased formazan content of myocardium, reduced LDH release, improved the recovery of the left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure, left ventricular end-diastolic pressure and rate pressure product （left ventricular developed pressure multiplied by heart rate） and attenuated the decrease of coronary flow during reperfusion. Administration of atractyloside （20 μmol/L）, an opener of mitochondrial permeability transition pore, for 20 min （first 20 min of reperfusion） and 5-hydroxydecanoate （100 μmol/L）, the mitochondrial specific KATp blocker, for 20 min before ischemia attenuated the protective effects of Pue. Conclusion： The findings indicate that in the isolated rat heart, Pue protects myocardium against ischemia/ reperfusion injury via the opening of mitochondrial ATP-sensitive potassium channel and the inhibition of mitochondrial permeability transition pore opening.

关 键 词：葛根素 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：R363.2[医药卫生—病理学]