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/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)‐1β and 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 FPR2 receptor.
Cited
)
