缺血/再灌注损伤对大鼠心肌内源性可溶性糖基化终末产物受体分泌的影响  

Effects of myocardial ischemia/reperfusion injury on the level of endogenous soluble receptor for advanced glycation end-products(sRAGE)

作　　者：董洪武[1,2] 郭彩霞[1] 杜凤和[1] 王红霞[3] 曾翔俊[3] 张立克[3] 田俊萍[1] 

机构地区：[1]首都医科大学附属北京天坛医院心内科,北京100050 [2]首都医科大学教学医院北京石景山医院心内科,北京100043 [3]首都医科大学基础医学院病理生理教研室,北京100069

出　　处：《首都医科大学学报》2011年第5期640-644,共5页Journal of Capital Medical University

基　　金：国家自然科学基金项目(30801217)~~

摘　　要：目的观察在体大鼠心肌缺血/再灌注(ischemia/reperfusion,I/R)及离体培养心肌细胞单纯缺氧(hypoxia,H)或缺氧/复氧(hypoxia/reoxygenation,H/R)损伤时,血浆或培养基中可溶性糖基化终末产物受体(soluble receptor for advanced glycationend-products,sRAGE)含量的变化,了解缺血/再灌注对内源性sRAGE的影响。方法采取结扎冠状动脉左前降支的方法复制在体大鼠心肌缺血/再灌注损伤模型,分别测定缺血前10 min(BI-10)、缺血45 min时(I-45)、再灌注60 min时(R-60)、再灌注120min时(R-120)和再灌注180 min时(R-180)的左室功能指标,包括心率(heart rate,HR)、左室收缩末压(left ventricular end systolicpressure,LVESP)、左室内压最大上升/下降速率(the maximum rate change of left ventricular pressure,±LVdp/dtmax);采用TTC染色法测定心肌梗死范围;采用酶联试剂盒测定血浆sRAGE浓度。培养乳鼠心肌细胞,复制缺氧/复氧损伤(H/R)模型,测定培养基sRAGE浓度和应用比色法测定乳酸脱氢酶(lactate dehydrogenase,LDH)活力。结果与假手术(sham)组相比较,I/R组I-45、R-60、R-120、R-180各时间点的HR、LVESP、±LVdp/dtmax均降低;在I/R组内,与BI-10相比,I-45、R-60、R-120、R-180各时点的sRAGE含量均降低。与control组相比,离体心肌细胞H(H/R)组的sRAGE含量差异无统计学意义。结论 I/R损伤血浆sRAGE含量降低,这可能与心肌缺血/再灌注损伤有关;而内源性sRAGE改变可能不是心肌细胞源性的。Objective We evaluated the plasma levels of soluble receptor for advanced glycation end-products（sRAGE） of the cardiomyocytes in vivo undergoing ischemia/reperfusion（I/R） injury and the medium levels of sRAGE of cardiomyocytes in vitro undergoing hypoxia（H） or hypoxia followed by reoxygenation（H/R）. Methods The rat model of myocardial I/R injury was induced by ligation of anterior descending coronary artery.All SD rats were randomly divided into two groups as follows： I/R group and sham group.The changes of heart rate（HR）,left ventricular end-systolic pressure（LVESP） and the maximum rate change of left ventricular pressure（±LVdp/dtmax） in the different time points（10 minutes before ischemia,the end of 45 minutes＇ ischemia,the end of 60 minutes＇ reperfusion,the end of 120 minutes＇ reperfusion and the end of 180 minutes＇ reperfusion,for short BI-10,I-45,R-60,R-120,R-180） were observed and analyzed.Infarction size was measured by tri-phenyltetrazolium chloride（TTC） staining.The levels of sRAGE were determined by enzyme linked immunoabsorbent assay.The isolated cardiomyocytes were randomly divided into two groups as follows： H or H/R groups and control groups.Lactate dehydrogenase（LDH） release was determined by an enzyme activity assay kit（Nanjing Institute of Jiancheng Bioengineering,Nanjing,China）. Results In the period of ischemia and reperfusion（I-45,R-60,R-120,R-180）,the left ventricular function（HR,LVESP,±LVdp/dtmax） in I/R group decreased compared with control group.Within I/R group,the left ventricular function and the levels of sRAGE in the different time points（I-45,R-60,R-120,R-180） were decreased as compared with BI-10.There is no statistical differences in the sRAGE levels between H or H/R groups and control groups. Conclusion Our findings indicate that the levels of sRAGE were reduced after I/R injury and suggest that the molecules of sRAGE were involved in the pathophysiological of myocardial I/R injury.

关 键 词：可溶性糖基化终末产物受体 缺血/再灌注损伤 心肌 

分 类 号：R363[医药卫生—病理学]