摘要
目的探讨地塞米松对哮喘小鼠中性粒细胞性气道炎症和高迁移率族蛋白B1(HMGB1)表达的影响。方法40只SPF级雌性Balb/c小鼠随机分为对照组、哮喘组、1 mg/kg地塞米松干预组、5 mg/kg地塞米松干预组,每组10只,采用无鸡蛋卵清蛋白诱导建立哮喘模型。采用小鼠有创肺功能仪测定小鼠气道高反应性;检测小鼠支气管肺泡灌洗液(BALF)中炎性细胞的数量及分类;HE染色观察肺组织病理学变化;免疫组化和Western blotting检测小鼠气道上皮及肺组织HMGB1的表达。结果与对照组比较,哮喘组小鼠气道反应性明显增强(P<0.01),BALF中炎性细胞总数明显增加,且以中性粒细胞为主(P<0.001),气道周围大量炎性细胞浸润,上皮细胞不同程度坏死脱落,气道上皮及肺组织HMGB1表达明显增加(P<0.05)。与哮喘组比较,地塞米松干预组小鼠气道反应性降低(P<0.05),BALF中炎性细胞总数和中性粒细胞计数均减少(P<0.01),气道周围炎性细胞浸润明显减少,气道炎症明显减轻,气道上皮及肺组织HMGB1表达差异无统计学意义(P>0.05)。结论以中性粒细胞性气道炎症为主的哮喘小鼠气道上皮及肺组织中HMGB1表达明显增加,地塞米松干预后,哮喘小鼠仍表现出较强的中性粒细胞性气道炎症及肺组织HMGB1高表达,提示HMGB1可能与哮喘中性粒细胞性气道炎症和糖皮质激素抵抗有关。
Objective To investigate the effect of dexamethasone intervention on neutrophil airway inflammation and high mobility group box 1 protein(HMGB1)expression in asthmatic mice.Methods Forty healthy SPF grade female Balb/c mice were randomly divided into four groups(n=10):Control group,Asthma group,1 mg/kg dexamethasone intervention group and 5 mg/kg dexamethasone intervention group.The asthmatic mice model was induced by egg-free ovalbumin.The airway hyper-responsiveness was measured by the invasive pulmonary function instrument;the number and classification of inflammatory cells in bronchoalveolar lavage fluid(BALF)were detected;lung pathological changes were observed by HE staining;HMGB1 expression was detected by immunohistochemistry and Western blotting.Results Compared with Control group,the airway responsiveness of asthmatic mice was significantly enhanced(P<0.01),the inflammatory cells in BALF were significantly increased,and neutrophils are the main cell types(P<0.001),a large number of inflammatory cells infiltrated around the airway,epithelial cells necrotized and shed in different degrees,and the expression of HMGB1 in airway epithelium and lung tissue increased significantly(P<0.05).Compared with Asthma group,the airway hyperresponsiveness decreased significantly after dexamethasone intervention(P<0.05),the total number of inflammatory cells and neutrophils in BALF were lower after dexamethasone intervention(P<0.01),the infiltration of inflammatory cells around the airway decreased significantly,and there was no significant difference between the expression of HMGB1 in airway epithelium and lung tissue(P>0.05).Conclusions The expression of HMGB1 in airway epithelium and lung tissue of asthmatic mice with neutrophilic airway inflammation was significantly increased.After dexamethasone intervention,asthmatic mice still showed higher neutrophilic airway inflammation and expression of HMGB1 in lung tissue,suggesting that HMGB1 may be associated with neutrophilic airway inflammation and glucocorticoid resistance in asthma.
作者
苏艳新
张明香
刘莎
王婷
谢军
邹文静
阮玲英
罗征秀
符州
Su Yan-Xin;Zhang Ming-Xiang;Liu Sha;Wang Ting;Xie Jun;Zou Wen-Jing;Ruan Ling-Ying;Luo Zheng-Xiu;FuZhou(Department of Emergency,the First Affiliated Hospital of Chongqing Medical University,Chongqing 400014,China;Department of Respiratory,Children’s Hospital of Chongqing Medical University/Ministry of Education Key Laboratory of Child Development and Disorders/National Clinical Research Center for Child Health and Disorders(Chongqing)/China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Children’s Hospital of Chongqing Medical University/Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China)
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2020年第2期171-175,共5页
Medical Journal of Chinese People's Liberation Army
基金
国家自然科学基金(81670018).
