齐留通干预ALOX5对RSV感染后小鼠气道炎症与AHR的影响  

Zileuton alleviates the airway inflammation and AHR in RSVinfected mouse by interfering ALOX5

作　　者：陈思思 于光远[2,3] CHEN Sisi;YU Guangyuan(Chongqing Medical and Pharmaceutical College,Chongqing 401331,China;Department of Respiratory Medicine,Children's Hospital of Chongqing Medical University,Chongqing 400014,China;Department of Respiratory Medicine,Guangzhou Women and Children's Medical Center,Guangzhou,Guangdong 510623,China)

机构地区：[1]重庆医药高等专科学校,401331 [2]重庆医科大学附属儿童医院呼吸中心,400014 [3]广州市妇女儿童医疗中心呼吸科,510623

出　　处：《免疫学杂志》2023年第4期305-311,共7页Immunological Journal

基　　金：国家自然科学基金(81900008);国家自然科学基金(82200011);重庆市自然科学基金(cstc2020jcyj-msxmX0303);重庆医药高等专科学校校级项目基金(ygz2022115)。

摘　　要：目的观察齐留通干预花生四烯酸5脂氧合酶(ALOX5)蛋白对呼吸道合胞病毒(RSV)感染引起的气道炎症与气道高反应性(AHR)的影响。方法6~8周雌性Balb/c小鼠随机分为对照组、RSV组和RSV+齐留通组,感染后第5天以Western blot检测各组肺组织中ALOX5蛋白水平。苏木精-伊红(HE)染色观察肺部病理损伤;检测各组小鼠支气管肺泡灌洗液(BALF)中细胞总数及分类计数;全身体积描述记法检测小鼠气道反应性;ELISA检测BALF中cys-LTs、IL-6、IL-8水平;探针法RTPCR检测肺组织中RSV A2 N基因拷贝数。结果RSV感染后第5天,小鼠肺组织中ALOX5蛋白水平升高,于齐留通干预后降低。齐留通可显著改善RSV感染后小鼠肺部病理损害、BALF中炎症细胞募集及AHR;齐留通干预后BALF中cys-LTs、IL-6、IL-8水平显著降低,但RSV N基因拷贝数无改变。结论齐留通可抑制ALOX5蛋白表达,减少炎症因子产生,改善RSV感染后小鼠气道炎症与AHR。This study was designed to observe the effect of zileuton on respiratory syncytial virus(RSV)-induced airway inflammation and airway hyperresponsiveness(AHR)by inhibiting arachidonate 5-lipoxygenase(ALOX5)protein in mice.Six to eight weeks old female Balb/c mice were recruited and randomly divided into control group,RSV group,and RSV+Zileuton group.ALOX5 protein levels in the lung tissue of those groups were detected by Western blotting on days 5 after RSV infection;the infiltration of inflammatory cells in lung tissues were detected by hematoxylin-eosin staining.The counts of total cells and different types of leukocytes in bronchoalveolar lavage fluid(BALF)were measured;AHR was measured by whole-body plethysmography;the levels of cysteinylleukotrienes(cys-LTs),interleukin-6(IL-6)and IL-8 were detected by ELISA;the copy numbers of RSV A2 N gene in the lung tissue were detected by probe RT-PCR.Data showed that the level of ALOX5 protein in lung tissue increased on day 5 after RSV infection and decreased after zileuton administration.Zileuton can significantly alleviate the pathological damage of lung tissue,inflammatory cell recruitment in BALF and AHR in RSV-infected mice.Meanwhile,the levels of cys-LTs,IL-6 and IL-8 in BALF were significantly decreased by zileuton,but the copy numbers of RSV N gene were not changed.In conclusion,zileuton can inhibit the expression of ALOX5 protein,reducing the production of inflammatory factors,thereby alleviating airway inflammation and AHR in mice after RSV infection.

关 键 词：齐留通 花生四烯酸5脂氧合酶 呼吸道合胞病毒 气道炎症 气道高反应性 

分 类 号：R725.6[医药卫生—儿科]