阿司匹林对小鼠心肌缺血/再灌注损伤时心肌组织炎症反应的影响  

Effects of aspirin on myocardial tissue inflammation in mice with myocardial ischemia/reperfusion injury

作　　者：张俊[1] 嵇富海[1] 孟晓文[1] 王辉[1] Zhang Jun;Ji Fuhai;Meng Xiaowen;Wang Hui(Department of Anesthesiology,the First Affiliated Hospital of Soochow University,Suzhou 215000,China)

机构地区：[1]苏州大学附属第一医院麻醉科,215006

出　　处：《国际麻醉学与复苏杂志》2021年第3期234-238,共5页International Journal of Anesthesiology and Resuscitation

基　　金：国家自然科学基金(81873925,82072130);江苏省自然科学基金(BK20191171)。

摘　　要：目的研究阿司匹林对小鼠心肌缺血/再灌注损伤(myocardial ischemia/reperfusion injury,MI/RI)时心肌组织炎症反应的影响。方法将60只雄性C57BL/6小鼠按随机数字表法分为3组(每组20只):假手术组(S组)、缺血/再灌注(ischemia/reperfusion,I/R)组(I/R组)、阿司匹林+I/R组(A+I/R组)。小鼠心肌I/R模型采用结扎左冠状动脉前降支(left anterior descending coronary artery,LAD)30 min后恢复血液灌注24 h建立。阿司匹林按100 mg/kg于术前2 h及再灌注结束前2 h通过腹腔注射分别给药。伊文蓝及2,3,5-氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)双染色法测定心肌梗死面积,H-E染色观察心肌组织病理改变。实时荧光定量PCR(real-time quantitative PCR,RT-qPCR)检测心肌组织中TNF-α、IL-1β、IL-6 mRNA水平,ELISA法测定血清阿司匹林诱生型脂氧素A4(15-epi-lipoxin A4,15-epi-LXA4)浓度,Western blot法检测心肌组织中甲酰肽受体2(formyl peptide receptor 2,FPR2)蛋白水平。结果与S组比较:I/R组和A+I/R组心肌缺血面积及心肌梗死面积增加,TNF-α、IL-1β、IL-6 mRNA水平升高,血清15-epi-LXA4水平升高(P<0.05);I/R组心肌损伤加重,炎症细胞浸润明显;A+I/R组FPR2蛋白水平升高(P<0.05)。与I/R组比较,A+I/R组心肌梗死面积减小,心肌损伤减轻,炎症细胞浸润减少,TNF-α、IL-1β、IL-6 mRNA水平降低,血清15-epi-LXA4水平升高,FPR2蛋白水平升高(P<0.05)。结论阿司匹林可减轻小鼠MI/RI,其机制可能与阿司匹林促进15-epi-LXA4合成以及激活FPR2受体发挥抗炎作用有关。Objective To investigate the effects of aspirin on myocardial tissue inflammation in mice during myocardial ischemia/reperfusion injury(MI/RI).Methods According to the random number table method,60 male C57BL/6 mice were divided into three groups(n=20):group sham operation(group S),group ischemia/reperfusion(group I/R)and group aspirin+ischemia/reperfusion(group A+I/R).A model of I/R in mouse myocardial tissues was established through occlusion of the left anterior descending coronary artery(LAD)for 30 min followed by reperfusion for 24 h.Aspirin was intraperitoneally injected at 100 mg/kg 2 h before operation and 2 h before the end of reperfusion.The infarct size was measured by Evans blue and 2,3,5-triphenyl tetrazolium chloride(TTC)double staining.The pathological changes of myocardial tissues were measured by hematoxylin-eosin(H-E)staining.The levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1βand IL-6 mRNA in myocardial tissues were detected by real-time quantitative PCR(RT-qPCR).The concentrations of serum 15-epi-lipoxin A4(15-epi-LXA4)were measured by enzyme-linked immunosorbent assay(ELISA).The levels of formyl peptide receptor 2(FPR2)were detected by Western blot.Results Compared with group S,groups I/R and A+I/R presented remarkable increases in ischemic and infarct sizes;increases in the levels of TNF-α,IL-1β,and IL-6 mRNA(P<0.05);and increases in the level of serum 15-epi-LXA4(P<0.05).Group I/R presented aggravated myocardial injury and obvious infiltration of inflammatory cells,while group A+I/R produced increased levels of FPR2 protein(P<0.05).Compared with group I/R,group A+I/R presented significantly reduced infarct size,relieved myocardial injury and reduced infiltration of inflammatory cells,as well as decreased levels of TNF-α,IL-1β,and IL-6 mRNA,increased concentrations of serum 15-epi-LXA4,and increased levels of FPR2 protein(P<0.05).Conclusions Aspirin relieves MI/RI in mice,which may be related to its inflammatory effects through stimulating 15-epi-LXA4 synthesis and activating

关 键 词：阿司匹林 心肌 缺血/再灌注损伤 脂氧素类 炎症反应 

分 类 号：R965[医药卫生—药理学]