ERK通路在缺血后处理保护缺血再灌注大鼠心肌间质中的作用  

Ischemic Postconditioning Ameliorates Myocardial Interstitial Injury in Rat Hearts with Ischemia/Reperfusion through Activation of ERK1/2 Pathway

作　　者：卢彦珍[1] 王佳[2] 宋娟[1] 张翠英[3] 冀菁荃[1] 宋晓亮[4] 

机构地区：[1]山西省长治医学院病理生理学教研室 [2]山西省长治医学院,免疫学教研室 [3]山西省长治医学院,生理学教研室 [4]山西省长治医学院,药理学教研室

出　　处：《中国分子心脏病学杂志》2013年第6期755-758,共4页Molecular Cardiology of China

基　　金：山西省自然科学基金资助项目(No.2009011055)

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。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.

关 键 词：缺血后处理 缺血-再灌注损伤 基质金属蛋白酶 细胞外信号调节蛋白激酶 

分 类 号：R363[医药卫生—病理学]