摘要
目的探讨左西孟旦后处理是否具有减轻心肌缺血再灌注损伤的作用及其可能的机制。方法通过结扎冠状动脉前降支40min、开放180min的方法建立心肌缺血再灌注模型。健康普通级成年雄性家兔42只,随机分为4组:假手术组(n=6)丝线从左冠状动脉前降支(LAD)下方穿过但不结扎;对照组(n=12)再灌注前10min时耳源静脉缓慢推注生理盐水;左西孟旦后处理组(n=12)再灌注前10min时耳源静脉缓慢推注左西孟旦0.1μmol·kg-1(0.1μmol·ml-1);格列苯脲组(n=12)先给予格列苯脲[ATP敏感的钾通道(KATP)非特异的阻断剂]0.33mg·kg-1,再给予左西孟旦0.1μmol·kg-1。分别在缺血前、缺血40min、再灌注180min末检测兔血浆磷酸肌酸激酶(CK)和丙二醛(MDA)活性;实验结束时,测定各组心肌梗死程度,检测心肌组织中髓过氧化物酶(MPO)的活性,并取近心尖左室心肌行HE染色,光镜观察。结果左西孟旦后处理组的心肌梗死程度为21.6%±1.75%,明显低于对照组(38.8%±1.88%)和格列苯脲组(40.8%±2.27%)。再灌注180min末,左西孟旦后处理组血浆CK和MDA活性明显低于对照组(P<0.01)和格列苯脲组(P<0.01);左西孟旦后处理组心肌组织中MPO活性明显低于对照组(P<0.05)。光镜观察发现左西孟旦后处理组心肌结构破坏程度较对照组和格列苯脲组明显减轻。结论对于缺血心肌,在再灌注前给予左西孟旦后处理可以减轻心肌的损伤,减少心肌梗死程度;这种保护作用可能与左西孟旦开放KATP、减轻Ca2+超载和氧化损伤有关。
Objective To explore the effects of postconditioning of levosimendan on ischemia and reperfusion injury in rabbits and it＇s potential mechanism involved.Methods The model of ischemia reperfusion was carried out by ligation of left anterior coronary descending branch（LAD） for 40min and removing the ligation for 180min.Forty-two anesthetized adult male rabbits were randomly divided into four groups：sham group（n=6）,left anterior coronary descending branch only exposed but not ligated for 220min;control groups（n=12）,isotonic Na chloride was given intravenously 10min before the reperfusion;levosimendan postconditioning group（n=12）,levosimendan 0.1μmol·kg-1 was given intravenously 10min before the reperfusion;glibenclamide group（n=12）,the same as levosimendan postconditioning group,but glibenclamide （0.33mg·kg-1） was given intravenously before levosimendan.Plasma creative kinase（CK） activity and malondialdehyde（MDA） activity were measured at baseline,the end of ischemia of 40min,and after 180min of reperfusion respectively.In the end of the experiment,the myocardial infarct size and tissue myeloperoxidase（MPO） activity were determined.The hearts were examined by microscope after using HE staining.Results Myocardial infarct size was significantly reduced in levosimendan postconditioning group（21.6%±1.75%） compared to control group（38.8%±1.88%） or glibenclamide group（40.8%±2.27%）.Plasma CK activity and MDA activity in levosimendan postconditioning group were significantly less than those in control group or glibenclamid group at 180min of reperfusion（all P〈0.01）.MPO activity of the ischemic area in levosimendan postconditioning group was less than that in control group（P〈0.05）.Light microscopic examination showed that the disorganization of myocardium was much slighter in levosimendan postconditioning group than that in control group or glibenclamide group.Conclusions As to ischemic myocardium,postconditioning of levosimendan could provide potent myocardial infarct size reduction and cardio-protective effect.The potential mechanism of this phenomenon might be associated with decresing the injury by activating KATP,avoiding Ca2＋ overload and decreasing peroxidation.
出处
《现代医学》
2009年第3期200-204,共5页
Modern Medical Journal
