作　　者： (王娅）; (刘明珠）; (李红俊）; (张蔚屏）; (高琴）; (李正红）;

机构地区： 蚌埠医学院生理学教研室,安徽蚌埠233030

出　　处： 《南方医科大学学报》 2017年第8期1028-1034,共7页

摘　　要： 目的探讨在大鼠心肌缺血再灌注过程中,内吗啡肽-1后处理的心肌保护作用对细胞外信号调节激酶1/2(Erk1/2)信号转导通路的影响。方法构建在体大鼠心肌缺血再灌注模型,分假手术组、缺血再灌注组、内吗啡肽-1后处理组(EM50组)、PD98059后处理组(PD组)、内吗啡肽-1+PD98059后处理组(EM50+PD组)。实时记录各组大鼠血流动力学指标,采集复灌结束后大鼠血清,检测超氧化物歧化酶、丙二醛、白介素-6、肿瘤坏死因子-α乳酸脱氢酶、肌酸激酶、心肌肌钙蛋白等心肌酶学及生化指标,大鼠心肌组织HE病理染色,TTC双染色法测定心肌梗死面积,Western-blot检测各组心肌组织中P-Erk1/2及凋亡相关蛋白Cleaved caspase-3的变化。结果与假手术组比较,缺血再灌注组心率和血压降低(P<0.05);与缺血再灌注组比较,EM50组心率和血压有所增高(P<0.05),血浆中乳酸脱氢酶、肌酸激酶、心肌肌钙蛋白、丙二醛、白介素-6、肿瘤坏死因子-α活性或含量下降;超氧化物歧化酶活性增加(P<0.05);心肌梗死面积减少(P<0.05);P-Erk1/2表达增加(P<0.05);Cleaved Caspase-3表达降低(P<0.05)。与EM50组比较,EM50+PD组心率和血压降低(P<0.05),血浆中乳酸脱氢酶、肌酸激酶、心肌肌钙蛋白、丙二醛、白介素-6、肿瘤坏死因子-α活性或含量增加,超氧化物歧化酶活性降低(P<0.05);心肌梗死面积增加(P<0.05);P-Erk1/2表达降低(P<0.05);Cleaved Caspase-3表达增加。结论内吗啡肽-1后处理可能通过改善心功能、抑制炎症反应、抑制氧化应激发挥保护作用;内吗啡肽-1改善大鼠心肌缺血再灌注损伤的过程中,存在Erk1/2信号通路的激活。 Objective To investigate the effect of postischemic treatment with endomorphin-1 （EM-1） against myocardial ischemia/reperfusion （IR） injury in rats and on extracellular signal regulated kinase 1/2 （Erk1/2）-dependent signaling pathway. Methods Sprague-Dawley rats were randomly divided into 5 groups, namely the sham-operated group, IR group, EM-1 post-treatment group （EM50 group）, EM-1 post-treatment group with PD98059 treatment （EM50＋PD group）, and PD98059 post-treatment group （PD group）. The hemodynamic indexes of the rats were recorded. After reperfusion, CK-MB, LDH, CTnI, MDA, IL-6, TNF-α, and SOD activities or contents were measured, the infarct size was determined, and the expression levels of Erk1/2, P-Erk1/2 and cleaved caspase-3 were detected using Western blotting. Results Compared with the sham group, the IR group showed significantly decreased heart rate and mean arterial pressure （P〈0.05）, which were increased obviously by EM-1 post-treatment （P〈0.05）. EM-1 post-treatment also resulted in significantly decreased LDH, CK-MB, CTnI, MDA, IL-6, and TNF-αactivities or contents （P〈0.05）, increased SOD activity （P〈0.05）, reduced the infarct size （P〈0.05）, and increased the expression level of P-Erk protein （P〈0.05）. Compared with EM50 group, EM50＋PD group showed significantly decreased heart rate and mean arterial pressure （P〈0.05）, increased LDH, CK-MB, CTnI, MDA, IL-6, and TNF-αactivities or contents （P〈0.05）, decreased SOD activity, increased infarct size （P〈0.05）, and lowered expression of P-Erk protein （P〈0.05）. Conclusion Postischemic treatment with EM-1 protects the heart against IR injury by improving the cardiac function, inhibiting inflammation, and inhibiting oxidative stress and myocardial apoptosis, and Erk1/2 signaling pathway may be involved in this process.

关 键 词： 细胞外信号调节激酶 心肌缺血后处理 心肌保护 内吗啡肽