芳香烃受体在内毒素诱发大鼠肺损伤时Clara细胞分泌蛋白表达下调中的作用  

Role of aryl hydrocarbon receptor in down-regulation of Clara cell secretory protein expression during endotoxin-induced lung injury in rats

作　　者：封珊[1] 李丹丹[1] 崔如 靖博雅 王云鹏 成翕悦[1] 李海滨[1] 阎锡新[2] Feng Shan;Li Dandan;Cui Ru;Jing Boya;Wang Yunpeng;Cheng Xiyue;Li Haibin;Yan Xixin(Department of General Medicine,the Third Hospital of Hebei Medical University,Shijiazhuang 050051,China;The First Department of Pulmonary and Critical Care Medicine,the Second Hospital of Hebei Medical University Hebei Key Laboratory of Respiratory Critical Care,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第三医院全科医学科,石家庄050051 [2]河北医科大学第二医院呼吸与危重症医学一科河北省呼吸危重症重点实验室,石家庄050000

出　　处：《中华麻醉学杂志》2023年第5期625-628,共4页Chinese Journal of Anesthesiology

基　　金：河北省医学科学研究重点课题计划项目(20190602)。

摘　　要：目的:评价芳香烃受体(AhR)在大鼠内毒素性肺损伤时Clara细胞分泌蛋白(CCSP)表达下调中的作用。方法:清洁级健康雄性SD大鼠24只,8周龄,体质量200~250 g,采用随机数字表法分为4组(n=6):正常对照组(C组)、ALI组、ALI+AhR拮抗剂组和ALI+溶剂组。采用气管内注入LPS 1 mg/kg的方法制备内毒素性肺损伤模型,注入LPS前2 h时,ALI+AhR拮抗剂组腹腔注射AhR拮抗剂6,2′,4′-三甲氧基黄酮溶液5 mg/kg(6,2′,4′-三甲氧基黄酮加溶剂二甲基亚砜配成1 ml溶液),ALI+溶剂组腹腔注射二甲基亚砜溶液1 ml。给予LPS后48 h时麻醉下处死大鼠,采用酶联免疫法测定左肺支气管肺泡灌洗液(BALF)CCSP浓度,采用免疫组化法测定右肺组织支气管上皮CCSP表达。结果:与C组比较,其余3组支气管上皮CCSP表达下调,BALF中CCSP浓度降低(P<0.05或0.01);与ALI组和ALI+溶剂组比较,ALI+AhR拮抗剂组组织病理学损伤减轻,支气管上皮CCSP表达上调,BALF中CCSP浓度上升(P<0.01)。结论:大鼠内毒素性肺损伤时AhR部分介导了CCSP的表达下调。Objective To evaluate the role of aryl hydrocarbon receptor(AhR)in the down-regulation of Clara cell secretory protein(CCSP)expression during endotoxin-induced lung injury in rats.MethodsTwenty-four clean-grade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 200-250 g,were divided into 4 groups(n=6 each)using a random number table method:normal control group(group C),acute lung injury(ALI)group,ALI+AhR antagonist group,and ALI+vehicle group.Lipopolysaccharide(LPS)1 mg/kg was intratracheally instilled to develop the model of lung injury,while the equal volume of normal saline was given instead in group C.At 2 h before LPS injection,AhR antagonist 6,2′,4′-trimethoxyflavone solution 5 mg/kg(diluted to 1 ml in dimethyl sulfoxide solution)was intraperitoneally injected in ALI+AhR antagonist group,while dimethyl sulfoxide solution 1 ml was given in ALI+vehicle group.The rats were sacrificed under anesthesia at 48 h after LPS administration.The left lung was lavaged and the broncho-alveolar lavage fluid(BALF)was collected for determination of the concentrations of CCSP by enzyme-linked immunosorbent assay,and the expression of CCSP in the bronchial epithelium in right lung tissues was determined by immunohistochemistry.ResultsCompared with group C,the expression of CCSP in the bronchial epithelium was significantly down-regulated,and the concentrations of CCSP in BALF were decreased in the other three groups(P<0.05 or 0.01).Compared with ALI group and ALI+vehicle group,the histopathological injury was significantly reduced,the expression of CCSP in the bronchial epithelium was up-regulated,and the concentrations of CCSP in BALF were increased in ALI+AhR antagonist group(P<0.01).ConclusionsAhR partially mediates the down-regulation of CCSP expression during endotoxin-induced lung injury in rats.

关 键 词：受体 芳基烃 内毒素类 急性肺损伤 CLARA细胞分泌蛋白 

分 类 号：R563[医药卫生—呼吸系统]