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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。
Objective To investigate the role of extracellular signal-regulated kinase 1/2 (ERK1 / 2) pathway in reducing ischemic / reperfusion myocardial interstitium damage in rats after ischemic postconditioning. Methods Thirty-two healthy male Sprague-Dawley rats were randomly divided into four groups: sham operation group (SC group), ischemia reperfusion group (I / R group), ischemic postconditioning group (IPTC group), ERK1 / 2 inhibitor PD98059 Group (PD group). The changes of left ventricular hemodynamics were recorded. The content of myocardial collagen was measured. The levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in plasma were measured. The protein levels of ERK1 / 2, p-ERK1 / 2 and MMP-2 in myocardium were detected by Western blot. The expression of MMP-2 was detected by RT-PCR. Results Compared with I / R group, the level of p-ERK1 / 2, the content of myocardial collagen and the left ventricular systolic and diastolic function in IPTC group were significantly increased, while the activity of MMP-2 protein and mRNA, ; The expression of p-ERK1 / 2 in myocardium was decreased with the ERK1 / 2 inhibitor PD98059, the activity of MMP-2 protein and its expression in myocardium and the activity of plasma CK and LDH were significantly increased. The content of collagen and the function of left ventricular systolic and diastolic were significantly decreased. Conclusion Ischemic postconditioning can protect the myocardial interstitium through the activation of ERK1 / 2 signaling pathway and the alteration of MMP-2 activity.