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

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（1／R组）、缺血后处理组（IPTC组）、ERK1／2抑制剂PD98059组（PD组）。记求各组在室血流动力学变化，观察心肌胶原含量，测定血浆中肌酸激酶（CK）和乳酸脱氧酶（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ERK1／2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。

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

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.