扎考必利后处理对离体大鼠心脏的保护作用

The protection of Zacopride postconditioning against the reperfusion injury in rat hearts

目的观察内向整流钾离子(IK1)通道激活剂扎考必利在缺血后处理中的作用并探讨可能存在的有关机制。方法24只大鼠离体心脏,随机分为非缺血组,缺血再灌组和扎考必利后处理组,分别进行灌注Krebs–Henseleit(K-H)液60min;缺血30 min再灌注K-H液30 min;缺血30 min再灌注含1μmol/L扎考必利的K-H液5 min后改用不含扎考必利的KH液灌注25 min。记录心率(HR),左室发展压(LVDP),左室内压的最大上升下降速率(±dp/dt max)等血流动力学数据,冠脉流速(CF)和心律失常情况。再灌注结束后测量冠脉流出液中的肌钙蛋白I(cTnI),丙二醛(MDA),总超氧化物歧化酶(TSOD)含量,并用2,3,5—氯化三苯基四氮唑(TTC)染色测心梗面积。结果与缺血再灌注组相比,扎考必利后处理组可增加缺血再灌注30 min时的HR,LVDP,+dp/dtmax,CF,减少心律失常的发生并减少cTnI及MDA的生成,增加SOD的活性,减少心梗面积。结论扎考必利后处理可以有效减轻再灌注后心肌损伤,保护心脏收缩功能和减少心律失常的发生。

Objective To observe the effect of zacopride,an inward rectifier potassium （IK1） channel agonist,in the postconditioning against myocardial ischemia reperfusion injury and to explore its mechanisms.Methods 24 isolated lagendorff rat hearts were randomly divided into non-ischemia group （NI group,n =8）,ischemia/reperfusion group （IR group,n =8） and zacopride postconditioning group （ZP group,n=8）.Krebs-Henseleit （K-H） buffer was perfused for 60 min in NI group.In IR group,after a period of 30 min ischemia,K-H buffer was perfused for 30 min.While in the ZP group,after a period of 30 min ischemia,K-H buffer containing 1 μmol/L zacopride was persued for 5 min,and then a period of 25 min normal K-H buffer perfusion was followed.Hemodynamic data of three groups including the heart rate （HR）,left ventricular developed pressure （LVDP）,maximum positive and negative derivative of left ventricular pressure （±dp/dtmax） and coronary flow （CF） were recorded.Coronary effluent was collected to measure the concentration of cardiac troponin Ⅰ （cTnⅠ）,malondialdehyde （MDA） and total superoxide dismutase （T-SOD）.Myocardial infarction size was measured by 2,3,5-triphenyl tetrazolium chloride （TTC） staining.Results Compared with that in the IR group,cardiac hemodynamic data of LVDP,＋dp/dtmax and CF in the ZP group was improved significantly.Compared whith that in the other two goups,the incidence of arrhythmia,the generation of cTnⅠ and MDA,and myocardial infarction size reduced significantly,and the SOD activity enhanced apparently in the ZP group.Conclusion Zacopride postconditioning can effectively reduce myocardial injury of ischemia reperfusion by increasing cardiac function and reducing the incidence of arrhythmia.