目的 探讨度洛西汀对大鼠心脏缺血再灌注心律失常的影响及机制.方法 30只Sprague Dawley (SD)大鼠随机分为假手术组(Sham组)、缺血再灌注组(IR组)和度洛西汀组(Dulo组).IR组大鼠左前降支结扎30min后再灌注120min,Dulo组大鼠结扎左前降支30min前腹腔注射盐酸度洛西汀40mg/kg,之后处理同IR组,Sham组仅暴露左前降支,未行结扎.二导联心电监测并记录3组心律失常发生情况,应用LabChart8软件分析心电图参数.Triphenyhetrazolium chloride(TTC)染色对比IR组及Dulo组大鼠心肌梗死面积.蛋白免疫印迹试验检测各组心脏组织Akt、细胞外调节蛋白激酶(extracellular regulated protein kinases,Erk)、caspase-3、超氧化物歧化酶(superoxide dismutase,SOD)1、SOD2和连接蛋白43(connexin 43,Cx 43)蛋白改变.结果 与IR组比较,缺血期Dulo组大鼠室性期前收缩次数和室性心动过速次数减少(P＜0.05);再灌注期Dulo组的室性心动过速减少(P＜0.05),室性期前收缩次数差异无统计学意义(P＞0.05).度洛西汀抑制缺血和再灌注所致校正后Q-T间期(QTc)的延长(P＜0.05),并减小心肌梗死面积(P＜0.05).度洛西汀抑制Akt和Erk蛋白的磷酸化,减少cleaved caspase-3、cy-tochrome C蛋白表达并增加SOD1、SOD2和Cx43蛋白表达.结论 度洛西汀降低Akt和Erk蛋白磷酸化,抑制氧化应激及细胞凋亡,减低心脏缺血再灌注损伤过程中室性心律失常发生,减少梗死面积.%Objective To explore the protective effects of duloxetine on ventricular arrhythmia in rats with ischemia reperfusion injury.Methods Thirty Sprague Dawley (SD) rats were randomly divided into 3 groups:Sham group,ischemia reperfusion group (IR group),duloxetine-treated group (Dulo group).The rats in IR group were subjected to 30min-ischemia of left anterior descending artery ligation followed by 120min of reperfusion,while intraperitoneal injection of duloxetine 40mg/kg were give prior ischemia in Dulo group,and the remaining experiment protocols were same as IR group.The left anterior descending artery of rats in sham group was exposed without being clamped.Two biopotential leads ECG monitor was used to record the arrhythmia in each group,and ECG parameters were analyzed by LabChart 8 software.Triphenyltetrazolium chloride (TTC) was used for determination of infarct area.The protein expressions of Akt,extracellular regulated protein kinases (Erk),caspase-3,superoxide dismutase (SOD) 1,SOD2 and Connexin 43 (Cx 43) were measured by western blot analysis.Results As compared to IR group,the incidences of both ventricular extrasystoles and tachycardia were decreased during ischemic period (P ＜0.05),and the incidence of ventricular tachycardia was decreased with no significant changes in ventricular extrasystoles during reperfusion period in Dulo group (P ＜ 0.05).Duloxetine decreased the prolonged QTc and infraeted area during IR injury (P ＜ 0.05).Duloxetine inhibited the phosphorylation of Akt and Erk,and downregulated the protein expressions of cleaved caspase-3,cytochrome C,while upregulated SOD1,SOD2 and Cx 43 protein expression during I/R injury (P ＜ 0.05).Conclusion Duloxetine decreases the phosphorylation of Akt and Erk,inhibits oxidative stress and apoptosis,exerts anti-arrhythmogenic effects and decreases the occurrence of ventricular arrhythmia and infracted area induced by myocardial IR.
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