尼可地尔后处理联合预处理对离体心肌缺血/再灌注的作用研究  

Effects of ischemic postconditioning and preconditioning induced by Nicorandil on myocardial ischemia/reperfusion injury in isolated rat heart

作　　者：鹿欣[1] 刘立群[2] 陈维宁[3] 崔玉倩[1] 王士忠[2] 都彩菊[2] 

机构地区：[1]山东省潍坊医学院,261042 [2]潍坊医学院附属医院胸心外科,261042 [3]山东省潍坊医学院药理学教研室,261042

出　　处：《中华临床医师杂志（电子版）》2007年第6期27-31,共5页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：目的探讨尼可地尔药物后处理、预处理,及二者联合对缺血再灌注损伤离体大鼠心肌的心肌梗死面积,冠脉流出液生化指标,及血流动力学的影响,为临床心脏疾病的治疗提供理论依据。方法48只大鼠随机分为6组,离体心脏Langendorff装置灌流,(1)对照组(Con):左冠前降支(LAD)阻断40min,复灌120min。(2)缺血后处理组(Pos):在复灌开始,LAD给予6次短暂开放/钳夹。(3)药物后处理组(Npo):尼可地尔(Nic)20μmol/L于复灌时给予10min。(4)药物预处理组(Ipc):在LAD阻断前先给予10min的Nic。(5)联合组(Npp):LAD阻断前后分别给予Nic。(6)阻滞剂组(Gnp):灌注液中含有格列本脲(Gli)20μmol/L。结果Pos、Npo、Ipc、Npp同Con比较,LVDP、±dp/dtmax、CF在复灌后各时间点增高(P<0.05),Gnp同Con比较差异无统计学意义(P>0.05)。Npp同Pos、Npo、Ipc比较未表现出叠加效应(P>0.05)。复灌30min后Pos、Npo、Ipc、Npp中CK、LDH漏出量较少(P<0.05),Con同Gnp比较差异无统计学意义。Npp同Pos、Npo、Ipc比较差异无统计学意义。Ipc中心肌梗死区重量从(50.02±2.9)%下降到(22.72±3.6)%(P<0.05),Npp和Npo梗死面积分别减小到(23.99±4.3)%和(29.02±2.1)%(P<0.05),Pos梗死面积为(34.63±4.1)%(P<0.05),Gli取消了Nic的保护作用,心肌梗死面积为(46.82±6.69)%(P>0.05)。结论缺血后处理,尼可地尔后处理、预处理,及尼可地尔后处理及预处理联合对离体大鼠心肌有保护作用,但尼可地尔后处理联合预处理未表现明显叠加作用。尼可地尔后处理的心肌保护效应可能与再灌注早期的K-ATP通道的激活密切相关。Objective To explore the effect of Nicorandil postconditioning and preconditioning and synergistic effect of both on myocardial I/R injury in isolated rat heart for measurement of the area at risk of infarction, biochemical indicator of effluent and hemodynamics index of cardiac function. Mefhods Langendorff isolated perfused rat heart were subjected to 30 min of local ischemia followed by 120 min reperfusion. All hearts were randomly divided into 6 groups. （ 1 ） （group CON）Control hearts underwent no additional intervention; （2） （ group POS） Posteonditioning consisted of 6 episodes of 10 seconds （s） of left anterior descending branch（LAD） occlusion and 10 s of reperfusion performed before full restoration of flow;（ 3 ） （group NPO）Nicorandil postconditioning group：the hearts were dealt as group CON, but during the reperfusion period the hearts were reperfused with liquid including Nicorandil（20 μmol/L） for 10 rain,and followed by 120 min of reperfusion; （4） （ group IPC i Nicorandil preconditioning was achieved by reperfusing liquid that contained Nicorandil for 10 rain before the ischemic; （5） （group NPP ）： Nicorandil preconditioning combined with N icorandil postconditioning; （6） （group GNP） ：the hearts were dealt as Nppbut the liquid including glibenclamide （ Gli ： 20 μmoL/L）. Observed indexes include ： 1 ） recovery of cardiac function including Lvdp, ＋ dp/dt;2） coronary flow（CF） ;3）myocardial CK leakage and LDH in the effluent from the isolated perfused heart; 5 ） The myocardial infarct size were evaluated by TTC staining. Results Cardioprotective effect in POS,NPO,IPC＇and NPP significantly improved LVDP and ＋ dP/dt and increased CF. Gli abolished the improvement of cardiac function and CF. POS, NPO, IPC and NPP showed less the dosage of CK leakage and LDH, but there was not statistical difference between group CON and GNP. IPC reduced infarct size from（50. 02 ±2.9）% to（22. 72±3.6）% （P 〈0. 05） ,the prote

关 键 词：缺血预处理 心肌 心肌再灌注损伤 尼可地尔 格列本脲 钾通道 

分 类 号：R541[医药卫生—心血管疾病]