ERK1/2在缺血后适应减轻糖尿病小鼠心肌再灌注损伤中作用  

The role of ERK1/2 in attenuating ischemia-reperfusion injury caused by ischemia postconditioning in isolated diabetes mellitus mouse hearts

作　　者：刘芬[1] 杨毅宁[1] 马依彤[1] 陈邦党[1] 李晓梅[1] 向阳[1] 黄莺[1] 谢翔[1] 

机构地区：[1]新疆医科大学第一附属医院心脏中心,新疆乌鲁木齐830011

出　　处：《新疆医科大学学报》2011年第6期559-563,共5页Journal of Xinjiang Medical University

基　　金：国家重点基础研究发展(973计划)项目(2010CB535013);新疆医科大学第一附属医院科研奖励基金(2009yfy02)

摘　　要：目的 研究缺血后适应对糖尿病小鼠离体心脏缺血再灌注损伤的作用及细胞外信号调节激酶(ERK1/2)在缺血后适应心肌保护中的作用。方法将C57/BL小鼠随机分为6组:(1)空白对照组(N组);(2)缺血再灌注组(I/R组);(3)缺血后适应组(Post组);(4)糖尿病小鼠空白组(DN组);(5)糖尿病小鼠缺血再灌注组(D I/R组);(6)糖尿病小鼠后适应组(D post组)。观察后适应对心脏血流动力学、梗死心肌范围的影响及与ERK1/2表达水平的关系。结果与I/R组比较,左室舒张末期压力(LVDP)、左心室压力变化最大速率和最小速率(+dp/dtmax和-dp/dtmax)恢复率明显增加(P<0.05)。而D Post组与DI/R组比较上述变化均不明显(P>0.05)。Post组心肌梗死范围较I/R组显著减小(P<0.01),D Post与DI/R组比较差异无统计学意义(P>0.05)。各组小鼠体重、心重指数无明显差异。各组体外心脏组织中ERK1/2总蛋白表达无明显差异(P>0.05)。但与I/R组比较,Post组心肌磷酸化ERK1/2水平明显增加(P<0.01)。D Post组的心肌磷酸化ERK1/2水平与DI/R组比较未见明显增加(P>0.05)。结论缺血后适应能有效地减轻离体小鼠心肌再灌注损伤,改善心功能,而在糖尿病小鼠中,这种保护作用并不明显。糖尿病小鼠缺血后适应保护作用减弱可能与其不能明显激活ERK1/2有关。Objectives To explore the effects of ischemia postconditioning（IPC） on ischemia-reperfusion（I/R） injury in isolated diabetes mellitus mouse hearts and investigate the role of ERK1/2.Methods All C57/BL mice were received following six group：（1） normal control（N）;（2） ischemia-reperfusion（I/R）;（3） ischemia postconditioning（Post）;（4） diabetes mellitus normal control（D N）;（5） diabetes mellitus ischemia-reperfusion（D I/R）;（6） diabetes mellitus ischemia postconditioning（D Post）.The effects of ischemia postconditioning on hemodynamics,coronary artery flow and myocardial infarction size were measured.Meanwhile,level of myocardial phosphor-protein kinase（p-ERK1/2） of myocardial tissue were evaluated.Results Hemodynamics was improved significantly in Post group but not in D Post group.The same result was reduced with significant reduction of myocardial infarction size in Post group as compared with IR group instead of D Post.Meanwhile,the level of p-ERK1/2 increased in Post group compared with those in IR control group,while it did not increase in D Post groups.Conclusion Ischemia postconditioning attenuates I/R injury of isolated mouse hearts.But in isolated diabetes mellitus mouse hearts,the roles did not discovered,because the ERK1/2-MAPK signal transduction decline is involved in mediating cardioprotection of diabetes mellitus mouse.

关 键 词：缺血后适应 小鼠心肌 再灌注损伤 

分 类 号：R34[医药卫生—基础医学] R-332