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目的探讨晚期糖基化终末产物受体(RAGE)与远端缺血后适应(IPOC)心肌缺血-再灌注(I-R)损伤的关系。方法 39只7~9周龄健康雄性C57BL/6J小鼠随机均分为假手术(A组)、I-R(B组)和IPOC(C组)三组。A组小鼠开胸,未对心脏做任何处理;B组小鼠结扎冠状动脉前降支,再灌注前后无特殊处理;C组在再灌注的初期对小鼠远端肢体行IPOC处理。采用小动物心超仪检测三组小鼠左心室射血分数(LVEF)和左心室缩短分数(LVFS);采用伊文氏蓝和三苯基氯化四氮唑缓冲液染色测定三组小鼠心肌梗死面积;采用Western blot法检测心脏组织中RAGE、高迁移率族蛋白1(HMGB1)、蛋白激酶B(AKT)和细胞外信号调节激酶1/2(ERK1/2)的表达。结果与A组比较,B组RAGE和HMGB1相对表达量增高(P<0.01)。与B组比较,C组RAGE和HMGB1相对表达量降低,磷酸化AKT(p-AKT)相对表达水平增高(P<0.05);与A组比较,B、C组p-ERK1/2相对表达水平均增高(P<0.05)。B组LVEF和LVFS低于A、C组(P<0.01或P<0.05)。与B组比较,C组心肌梗死面积减少(P<0.05)。结论远端IPOC处理能够改善由I-R损伤引起的心肌功能障碍,减少心肌梗死面积;RAGE和HMGB1可能参与了这一过程。
Objective To investigate the relationship between advanced glycation end-products receptor (RAGE) and ischemia-reperfusion injury (IPOC) and myocardial ischemia-reperfusion (I-R). Methods Thirty-nine healthy male C57BL / 6J mice aged 7-9 weeks were randomly divided into sham operation (group A), I-R (group B) and IPOC (group C). A group of mice thoracotomy, did not do any treatment of the heart; Group B mice ligation of coronary anterior descending artery, before and after reperfusion without special treatment; C group in the early reperfusion of distal limbs IPOC treatment. Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were measured in small animals by ultrasonography. The myocardium of the three groups was detected by Evan’s blue and triphenyltetrazolium chloride buffer The area of infarction was detected by Western blot. The expressions of RAGE, HMGB1, AKT and ERK1 / 2 in cardiac tissue were detected by Western blot. Results Compared with group A, the relative expression of RAGE and HMGB1 in group B was increased (P <0.01). Compared with group B, the relative expression of RAGE and HMGB1 in C group decreased and the relative expression of phosphorylated AKT increased (P <0.05). Compared with group A, the relative expression of p-ERK1 / 2 in group B and C (P <0.05). The LVEF and LVFS in group B were lower than those in group A and C (P <0.01 or P <0.05). Compared with group B, the area of myocardial infarction in group C decreased (P <0.05). Conclusion Remote IPOC treatment can improve myocardial dysfunction induced by I-R injury and reduce the area of myocardial infarction. RAGE and HMGB1 may be involved in this process.