【摘要】 目的:探讨脂氧素受体激动剂BML-111在肠缺血再灌注早期急性肺损伤中的作用及其机制。方法:32只8周龄健康雄性SD大鼠随机分为假手术组、缺血再灌注组、缺血再灌注+BML-111处理组(BML-111组)和缺血再灌注+Boc-2+BML-111处理组(Boc-2组),BML-111组和Boc-2组在再灌注开始时通过腹腔注射给予BML-111(1mg/kg),Boc-2组在麻醉后通过腹腔注射给予Boc-2(50μg/kg),另两组注入等量生理盐水。采用夹闭SD大鼠肠系膜上动脉45 min后再灌注6 h的方法造成肠缺血再灌注损伤模型。处死大鼠取肺标本,HE染色观察肺组织病理学改变,检测肺组织含水率;ELISA检测肺组织TNF-α、IL-1β和IL-6水平;蛋白质印迹法检测肺组织磷酸化p38 MAPK和NF-κB蛋白表达水平。结果 :肠缺血再灌注导致明显肺损伤,肺含水率增加,TNF-α、IL-1β和IL-6含量明显升高,p38 MAPK/NF-κB通路活化;BML-111可抑制肺组织p38 MAPK/NF-κB活化,减轻小肠缺血再灌注引起的肺损伤,并下调肺组织TNF-α、IL-1β和IL-6含量,当应用Boc-2处理后,BML-111的肺保护作用被取消。结论 :BML-111通过抑制p38 MAPK/NF-κB通路活化促进肠缺血再灌注早期肺损伤炎症消退。更多还原

【Abstract】 Objective This study aims to investigate the effect of Lipoxin A4 receptor on acute lung injury(ALI) induced by intestine ischemia-reperfusion(ⅡR).Methods Thirty-two 8-week old SD rats were randomly divided into four groups:sham,intestine ischemia-reperfusion(ⅡR),ⅡR + BML111(BML-111),Boc-2 + ⅡR +BML111(Boc-2).BML-111(1 mg/kg) was given intraperitoneally at the onset of reperfusion in the BML-111 and the Boc-2 group.Boc-2(50 μg/kg) was given intraperitoneally after anesthesia in the Boc-2 group.Rats were subjected to superior mesenteric artery occlusion consisting of 45-min ischemia and 6-h reperfusion,and the sham laparotomy was served as controls.The lung pathology was assayed by the H&E staining.Lung water content was detected using dry/wet ratio.Concentrations of TNF-α,IL-1β,and IL-6 in lung tissue were determined by ELISA.The protein expression of p38 MAPK and NF-kB of lung was assayed by western blot.Results ⅡR induced serious ALI,with poor lung pathology and increased lung water content,elevation of TNF-α,IL-1β,and IL-6 levels in lung,accompanied with activation of p38 MAPK/NF-κB pathway.However,BML-111 could inhibit the activation of p38 MAPK/NF-κB pathway,leading to the reductions of TNF-α,IL-1β,and IL-6 in lung and attenuation ofⅡR-induced ALI.Conclusion BML-111 treatment could attenuate inflammation in lung after ⅡR injury via inactivating the p38 MAPK/NF-κB signaling pathway.更多还原