促红细胞生成素减轻大鼠心肌缺血再灌注损伤  

Erythropoietin reduces myocardial ischemia-reperfusion injury in rats

作　　者：郭晋村[1] 黄卫斌[1] 王挹青[1] 谢良地 

机构地区：[1]厦门大学附属中山医院心内科,福建厦门361004 [2]福建省高血压研究所,福建福州350108

出　　处：《基础医学与临床》2010年第3期289-292,共4页Basic and Clinical Medicine

摘　　要：目的探讨促红细胞生成素在心肌缺血再灌注损伤中对细胞外基质代谢的调节作用及其机制。方法构建Langendroff大鼠离体心脏缺血再灌注模型,结合Western blot观测在促红细胞生成素及相应信号传导通路阻滞剂干预下,左室舒张末压(LVEDP)、梗死面积、MMPs及胶原Ⅰ/Ⅲ表达的变化。结果促红细胞生成素可改善LVEDP[(19.8±0.2)mmHgvs(35.9±0.2)mmHg,IR组vsEPO+IR组,P<0.05],减少梗死面积(35.26%±7.1%vs62.70%±7.2%,EPO+IR组vsIR组,P<0.05)。在缺血再灌注损伤的过程中MMP2及MMP9表达均显著升高,而TIMP-4则显著减低。外源性EPO可逆转MMPs的激活。此外EPO则可促进胶原Ⅲ、Ⅰ的表达,并且这一保护作用可被MEK-Erk信号通路阻滞剂所阻断。结论EPO通过MEK-Erk信号传导通路促进胶原Ⅰ/Ⅲ的合成,抑制MMPs的激活,抑制细胞外基质降解,在一定程度上减轻大鼠心肌缺血再灌注损伤。Objective To investigate the influence of erythropoietin in the metabolism of extracellular matrix after myocardial ischemia-reperfusion injury.Methods The langendroff reperfusion system was applied to investigate the protective function of EPO in ischemia-reperfusion condition in rats.The effects of EPO on extracellular matrix were observed by Western blot and signal pathway blocker.The LVEDP and infarction area were observed at the same time.Results EPO significantly improved LVEDP[（19.8±0.2）mmHg vs （35.9±0.2）mmHg,IR group vs EPO＋IR group,P0.05] and decreased infarction area （35.26%±7.13% vs 62.70%±7.23%,IR group vs EPO＋IR group,P0.05）.The expression of MMPs was significantly decreased and the expression of collagenaseⅠ/Ⅲ was significantly enhanced by EPO（MMP2 53.2＋2.6 vs 21.2＋2.5;MMP9 57.6±3.1 vs 19.2±2.6;IR group vs IR＋EPO group（P0.05）;collagenⅠ 43.2±2.2 vs 11.4±2.3;collagenⅢ 55.3±3.2 vs 18.1±2.3;IR＋EPO group vs IR group（P0.05）.This function can be inhibited by Mek-Erk inhibitor.Conclusion EPO plays a role in the metabolism of extracellular matrix by Mek-Erk signal pathway,which can protect the heart tissue from ischemia-reperfusion injury.

关 键 词：促红细胞生成素 细胞外基质 缺血再灌注损伤 

分 类 号：R541[医药卫生—心血管疾病]