孟鲁司特钠对支气管哮喘大鼠肺组织的影响及对核转录因子-κB通路的作用机制  

Effect of Montelukast Sodium on Lung Tissue of Asthmatic Rats and Its Mechanism of Action on Nuclear Factor-κB Pathway

作　　者：郭青[1] 刘珍 GUO Qing;LIU Zhen(Department of Respiratory Medicine,Children’s Hospital Affiliated to Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学附属儿童医院呼吸科,河南郑州450000

出　　处：《河南医学研究》2022年第12期2144-2148,共5页Henan Medical Research

基　　金：河南省医学科技攻关计划项目(LHGJ20190922)。

摘　　要：目的探讨孟鲁司特钠对支气管哮喘大鼠模型肺组织的保护作用机理及对核转录因子-κB(NF-κB)通路结构的影响。方法将40只4周龄Sprague-Dawley大鼠随机分为对照组、哮喘模型组、孟鲁司特钠低剂量组(5 mg·kg^(-1))、孟鲁司特钠高剂量组(10 mg·kg^(-1)),每组10只。通过卵白蛋白致敏并激发大鼠建立哮喘模型。在每次雾化前,给予孟鲁司特钠低剂量组、孟鲁司特钠高剂量组大鼠对应剂量的孟鲁司特钠混悬液灌胃,给予对照组和哮喘模型组生理盐水灌胃。记录各组大鼠进食量、饮水量、活动次数、抓鼻次数。采用酶联免疫吸附试验检测各组肺泡灌洗液中细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。采用蛋白免疫印迹法检测p-p65蛋白及NF-κB的抑制蛋白α(IκBα)表达水平。结果与对照组相比,哮喘模型组和孟鲁司特钠低剂量组每日进食量、饮水量减少,活动次数、抓鼻次数增加(P<0.05)。与对照组相比,哮喘模型组和孟鲁司特钠低剂量组IL-1β、IL-6、TNF-α水平较高(P<0.05)。与对照组比较,哮喘模型组p-p65表达上调,IκBα表达下调(P<0.05)。与哮喘模型组比较,孟鲁司特钠低剂量组和孟鲁司特高剂量组IL-1β、IL-6、TNF-α水平和p-p65表达水平较低,IκBα表达水平较高(P<0.05)。孟鲁司特钠低剂量组IL-1β、IL-6、TNF-α、p-p65、IκBα表达水平与孟鲁司特钠高剂量组比较,差异无统计学意义(P>0.05)。结论孟鲁司特钠可能通过选择性干扰NF-κB信号通路下游细胞因子的特异性表达减轻支气管哮喘大鼠肺组织的炎症反应。Objective To explore the protective mechanism of montelukast sodium on lung tissue of asthmatic rats and its effect on the structure of nuclear transcription factor-κB(NF-κB)pathway.Methods Forty 4-week-old Sprague-Dawley rats were randomly divided into control group,asthma model group,montelukast sodium low-dose group(5 mg·kg^(-1)),montelukast sodium high-dose group(10 mg·kg^(-1)),with 10 rats in each group.The asthma model was established through ovalbumin sensitization and and stimulation in rats.Before each atomization,rats in low-dose group and high-dose group of montelukast sodium were given corresponding doses of montelukast sodium suspension,and normal saline was given to control group and asthma model group.Food intake,water intake,activity times and nose scratching times of rats in each group were recorded.The levels of cytokines interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in alveolar lavage fluid of each group were detected by enzyme-linked immunosorbent assay.The expression levels of p-p65 and inhibitorαof NF-κB(IκBα)were detected by western blotting.Results Compared with control group,the daily intake of food and water in asthma model group and montelukast sodium low-dose group were decreased,and the activity times and nose scratching times of asthma model group and montelukast sodium low-dose group were increased(P<0.05).Compared with control group,the expression levels of IL-1β,IL-6 and TNF-α in asthma model group and montelukast sodium low-dose group were increased(P<0.05).Compared with control group,the expression of p-p65 was up-regulated and the expression of IκBα was down-regulated in asthma model group(P<0.05).Compared with asthma model group,the levels of IL-1β,IL-6,TNF-α and p-p65 in montelukast sodium low-dose group and montelukast sodium high-dose group were lower,but the expression level of IκBα was higher(P<0.05).The expression levels of IL-1β,IL-6,TNF-α,p-p65 and IκBα in montelukast sodium low-dose group were not different from tho

关 键 词：支气管哮喘 白三烯受体拮抗剂 核转录因子-ΚB 炎症反应 

分 类 号：R332.2[医药卫生—人体生理学]