【摘要】 目的探讨细胞外信号调节激酶1/2(ERK1/2)通路在缺血后处理减轻大鼠缺血/再灌注心肌间质损伤中的作用。方法 32只健康雄性SD大鼠随机分为4组,假手术组(SC组)、缺血再灌注组(I/R组)、缺血后处理组(IPTC组)、ERKl/2抑制剂PD98059组(PD组)。记录各组左室血流动力学变化,观察心肌胶原含量,测定血浆中肌酸激酶(CK)和乳酸脱氢酶(LDH)浓度。以Western blot法测定心肌组织中ERK1/2、p-ERK1/2和心肌基质金属蛋白酶-2(MMP-2)蛋白表达水平,以RT-PCR法从转录水平检测MMP-2的表达水平。结果与I/R组相比,IPTC组心肌p-ERK1/2水平、心肌胶原含量和左室舒缩功能明显升高,而心肌MMP-2蛋白表达及mRNA水平、血浆CK、LDH活力明显降低;使用ERKl/2抑制剂PD98059后,心肌p-ERK1/2表达水平下降,同时心肌MMP-2蛋白及表达、血浆CK、LDH活力明显增高,心肌胶原含量、左室舒缩功能明显降低。结论缺血后处理通过激活ERK1/2信号通路、改变MMP-2活性发挥保护缺血再灌注心肌间质的作用。更多还原

【Abstract】 Objective To investigate whether the extracellular signal-regulated kinase(ERK1/2) pathway is involved in cardioprotection by ischemic postconditioning in rat hearts with ischemia/reperfusion.Methods 32 healthy male Sprague-Dawley(SD) rats were randomly divided into 4 groups:sham control(SC) group,ischemic/reperfusion(I/R) group,ischemic postconditioning(IPTC) group,ERK1/2 inhibitor PD98059(PD) group.The left ventricular function including left ventricular pressure(LVP),left ventricular systolic pressure(LVSP) and its derivate(±dp/dt) was measured;The amount of myocardial collagen contents was determined by means of hydroxyproline quantification;the plasma activity of creatine kinase(CK) and lactate dehydrogenase(LDH) was detected;the protein level of total ERK1/2,phosphorylated ERK1/2 and matrix metalloproteinase-2(MMP-2) was measured by Western blot;the mRNA level of MMP-2 was detected by real-time PCR.Results The phosphorylated level of ERK1/2,the myocardial collagen contents and left ventricular function were significantly enhanced in IPTC group as compared with I/R group;the protein and mRNA level of MMP-2 and the activity CK and LDH in the plasma weresignificantly decreased in IPTC group when compared to I/R group;whereas the level of p-ERK1/2,the myocardial collagen contents and left ventri cular function were significantly reduced after addition of ERK1/2 inhibitor PD98059,the protein and mRNA level of MMP-2 and the activity CK and LDH in the plasma and were increased in PD group.Conclusion our results show that ischemic postconditioning exerts a potent myocardial interstitial protective effect on ischemia/reperfusion injury by reducing MMP-2 activity through the ERK signaling pathway.更多还原