摘要
目的:观察缺血后处理(IPost)对老年糖尿病大鼠心肌缺血再灌注(I/R)损伤的影响及蛋白酶激活受体2(PAR-2)活化对其保护作用。方法:老年雄性Wistar大鼠60只,随机选取45只采用链脲佐菌素(STZ)腹腔注射制备老年糖尿病大鼠模型,成模大鼠随机分成3组(每组15只):I/R组、IPost组、PAR-2作用组(PAR-2组);未行造模的另15只大鼠作为对照组(SC组)。SC组开胸后不结扎,旷置150min;I/R组结扎左冠状动脉前降支30min,再灌注120min;IPost组结扎左冠状动脉前降支30min后,再灌注10s,缺血10s,连续3个循环后,再灌注120min;PAR-2组缺血处理前1h尾静脉注射PAR-2激动剂(SLIGRL-NH2)激活PAR-2,其余处理同IPost组。之后下腔静脉采血,并摘取心脏,分析各组大鼠心肌组织细胞凋亡率、心肌梗死面积、血清超氧化物歧化酶(SOD)活性及丙二醛(MDA)浓度的差异。结果:与SC组比较,I/R组心肌梗死面积明显增加(P<0.01),心肌细胞凋亡率和MDA浓度升高(P<0.01),SOD活性下降(P<0.01);与I/R组比较,IPost组和PAR-2组心肌梗死面积缩小(P<0.05,P<0.01),心肌细胞凋亡率和MDA浓度下降(P<0.05,P<0.01),SOD活性升高(P<0.05,P<0.01)。PAR-2组较IPost组效果更明显(P<0.01)。结论:IPost对老年糖尿病大鼠心肌I/R损伤有保护作用,PAR-2活化可进一步增强此作用;其机制可能与其抑制再灌注诱导的细胞凋亡和氧化损伤有关。
Objective:To explore the effect of ischemic postconditioning on myocardial ischemia reperfusion injury in aged diabetic rats and the protective effect of protease-activated receptor 2(PAR-2)activation on myocardial ischemia reperfusion injury.Method:60healthy aged(22-24months)male Wistar rats were obtained.45 models of aged diabetic rats were induced by using streptozotocin(STZ)and then the diabetic rats were randomly divided into 3groups(15animals in each group):ischemia/reperfusion group(I/R group),ischemic postconditioning group(IPost group)and PAR-2group.In addition,another 15 rats were saline control group(SC group).The rats in SC group were only subjected to opening the chest but blood vessels were not ligated for 120 minutes.The rats in I/R group were induced by left anterior descending coronary artery occlusion for 30 minutes followed by 120 minutes of reperfusin.The rats in IPost group were treated by left anterior descending coronary artery occlusion for 30 minutes at first.Then left anterior descending coronary artery was released for 30 seconds and occluded for 30 seconds.This was repeated for 3cycles before the coronary artery was reperfused for 120 minutes.The rats in PAR-2group were subjected to IPost with further intervention.SLIGRL-NH2 was injected to activate PAR-2before 1hour.Difference of myocardial apoptosis,myocardial infarct size and levels of superoxide dismutase(SOD)and malonaldehyde(MDA)were analysed in each group.Results:In comparison with SC group,the myocardial infarct size was markedly increased(P〈0.01),the myocardial apoptosis index and the serum levels of MDA were increased(P〈0.01),but the serum levels of SOD were reduced(P〈0.01)in I/R group.Compared with I/R group,the myocardial infarct size was deereased,the myocardial apoptosis index and the serum levels of MDA were decreased while the serum levels of SOD were increased in IPost group(P〈0.05)and in PAR-2group(P〈0.01).The effect in PAR-2group was more remar
出处
《微循环学杂志》
2017年第1期1-5,共5页
Chinese Journal of Microcirculation
基金
湖北省自然科学基金(2014CKB1018)
关键词
蛋白酶激活受体2
缺血后处理
缺血再灌注损伤
老年糖尿病大鼠
心肌保护
Protease-activated receptor 2
Ischemic postconditioning
Ischemia reperfusion injury
Aged diabetic rats
Cardioprotection