RAGE阻断剂FPS-ZM1对心肌缺血再灌注损伤的作用研究  

Effect of RAGE blocker FPS-ZM1 on myocardial ischemia-reperfusion injury

作　　者：屠甜甜 王向明 狄瑞杰 郭妍 TU Tian-tian;WANG Xiang-ming;DI Rui-jie;GUO Yan(Department of Geriatric Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China)

机构地区：[1]南京医科大学第一附属医院老年心血管科,江苏省南京市210029

出　　处：《实用老年医学》2018年第5期425-429,共5页Practical Geriatrics

基　　金：江苏省自然科学基金项目(BK2011382);江苏省卫生厅科技项目(Z201301);江苏省六大人才高峰(2011-WS-029)

摘　　要：目的探讨晚期糖基化终末端产物受体(RAGE)阻断剂FPS-ZM1对心肌缺血再灌注损伤(MIRI)的作用及机制。方法将32只8~9周龄C57/B6小鼠随机分为4组:假手术组(sham组),FPS-ZM1对照组(FZM1组),缺血再灌注组(I/R组),FPS-ZM1干预组(FZM1+I/R组)。通过结扎冠状动脉前降支,建立小鼠心肌缺血再灌注模型。FPS-ZM1干预组小鼠手术前腹腔注射FPS-ZM1药物。采用小鼠心超仪检测血流动力学指标,运用苏木精-伊红(HE)染色法观察心肌组织的炎症程度,蛋白印迹法检测心脏组织中RAGE、高迁移率族蛋白B1(HMGB1)、P-ERK/ERK蛋白的表达。结果与sham组相比,I/R组心肌发生明显炎症,左室射血分数(LVEF)、左室缩短分数(LVFS)降低(P<0.05),RAGE、HMGB1(P<0.05)的表达水平明显增加;与I/R组相比,FPZM1+I/R组以上结果得到相反趋势。结论 FPS-ZM1能够通过抑制RAGE与HMGB1二者的结合,进而激活MAPK/ERK信号分子的表达来减轻MIRI的发生发展。Objective To investigate the effect of receptor for advanced glycation and products（ RAGE） blocker FPS-ZM1 on myocardial ischemia-reperfusion injury（ MIRI） and its mechanism.Methods Thirty-two C57/B6 mice aged 8-9 weeks were randomly divided into sham operation group（ sham group）,FPS-ZM1 control group（ FZM1 group）,ischemia/resperfusion group（ I/R group） and FPS-ZM1 intervention group（ FZM1 ＋I/R group）. The anterior descending coronary artery was ligated to create myocardial ischemia/reperfusion model of mouse. In FPS-ZM1 intervention group,the mice were injected intraperitoneally with FPS-ZM1 drug prior to surgery. The hemodynamics parameters were measured by using the mouse heart ultrasonography. The degree of myocardial infarction was determined by hematoxylin-eosin staining. The protein expressions of RAGE,HMGB1,P-ERK/ERK in heart tissue were detected by Western blotting. Results Compared with the sham group,the myocardium of I/R group showed obvious inflammation,LVEF,LVFS decreased（ P〈0. 05）,and the expression levels of RAGE and HMGB1 were increased significantly（ P〈0. 05）. Compared with I/R group,the above results of FZM1＋I/R group showed the opposite trend（ P〈0. 05）. Conclusions FPS-ZM1 can inhibit the combination of RAGE and HMGB1,and then activate the expression of MAPK/ERK signaling molecules to reduce the occurrence and development of MIRI.

关 键 词：缺血再灌注 FPS-ZM1 晚期糖基化终末产物受体 高迁移率族蛋白B1 

分 类 号：R542.2[医药卫生—心血管疾病]