鸢尾黄素对哮喘幼鼠气道炎症、气道重塑及HMGB1/TLR4/NF-κB通路的影响  

Effects of iris xanthin on airway inflammation,airway remodeling,and the HMGB1/TLR4/NF-κB pathway in asthmatic young mice

作　　者：李月云 王晓芳[1] 付艳[1] 王艳蕊[1] LI Yue-Yun;WANG Xiao-Fang;FU Yan;WANG Yan-Rui(Department of Pediatrics,Xinxiang Central Hospital,Xinxiang,Henan 453000,China)

机构地区：[1]新乡市中心医院儿科,河南新乡453000

出　　处：《中国当代儿科杂志》2024年第6期639-645,共7页Chinese Journal of Contemporary Pediatrics

基　　金：2023年度河南省医学科技攻关计划项目(LHGJ20230892)。

摘　　要：目的 探究鸢尾黄素对哮喘幼鼠气道炎症、气道重塑及高迁移率族蛋白B1 (high mobility group box1 protein,HMGB1)/Toll样受体4 (Toll-like receptor4,TLR4)/核因子κB (nuclear factor-κB,NF-κB)通路的影响。方法 将60只雄性BALB/c幼鼠随机分为空白组、模型组、地塞米松组,以及鸢尾黄素低、中、高剂量组,每组10只。采用腹腔注射致敏剂[卵清蛋白(ovalbumin,OVA) 20μg+氢氧化铝凝胶2 mg]+4%OVA雾化吸入激发建立幼鼠哮喘模型。肺功能检测仪检测幼鼠肺容积(lung volume,LV)、每分钟静息通气量(resting ventilation per minute,VE)及气道反应性(Penh值);苏木精-伊红染色观察并分析气道重塑情况;ELISA法检测肺泡灌洗液中白介素(interleukin,IL)-1β、IL-6、肿瘤坏死因子α (tumor necrosis factor alpha,TNF-α)含量;实时定量逆转录聚合酶链反应及Western blot法检测肺组织中HMGB1/TLR4/NF-κB通路相关mRNA及蛋白表达。结果 与模型组比较,地塞米松组及鸢尾黄素低、中、高剂量组LV、VE均显著升高(P<0.05),其中鸢尾黄素各剂量组随剂量增加LV、VE升高(P<0.05);地塞米松组及鸢尾黄素低、中、高剂量组Penh值、IL-1β、IL-6、TNF-α、气道重塑指标,以及HMGB1、TLR4、NF-κB p65 mRNA和HMGB1、TLR4、p-NF-κB p65蛋白表达水平均降低(P<0.05),其中鸢尾黄素各剂量组随剂量增加上述指标降低(P<0.05)。与地塞米松组比较,鸢尾黄素低、中剂量组LV、VE均降低(P<0.05),Penh值、IL-1β、IL-6、TNF-α、气道重塑指标,以及HMGB1、TLR4、NF-κB p65 mRNA和HMGB1、TLR4、p-NF-κB p65蛋白表达水平均升高(P<0.05);鸢尾黄素高剂量组上述指标与地塞米松组比较差异无统计学意义(P>0.05)。结论 鸢尾黄素能有效减轻哮喘幼鼠气道炎症,抑制气道重塑,可能与抑制HMGB1/TLR4/NF-κB通路有关。Objective To explore the effects of iris xanthin on airway inflammation,airway remodeling,and the high mobility group box 1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)pathway in asthmatic young mice.Methods Sixty male BALB/c young mice were randomly assigned into six groups:a blank group,a model group,a dexamethasone group,and low,medium,and high dose groups of iris xanthin,with ten mice per group.Asthma models were induced through intraperitoneal injections of a sensitizing agent[ovalbumin(OVA)20μg+aluminum hydroxide gel 2 mg],followed by 4%OVA aerosol inhalation.Lung function was measured using a pulmonary function tester to determine lung volume(LV),resting ventilation per minute(VE),and airway reactivity(Penh value).Hematoxylin-eosin(HE)staining was employed to examine and analyze airway remodeling.The contents of interleukin(IL)-1β,IL-6,and tumor necrosis factor alpha(TNF-α)in bronchoalveolar lavage fluid were quantified using ELISA.Real-time fluorescence quantitative polymerase chain reaction and Western blot analysis were used to assess the expression of HMGB1/TLR4/NF-κB pathway-related mRNA and proteins in lung tissues.Results Compared to the model group,the dexamethasone and iris xanthin-treated groups(low,medium,and high doses)exhibited significant increases in LV and VE(P<0.05),with incremental dose-dependent increases observed in the iris xanthin groups.Additionally,Penh values,IL-1β,IL-6,TNF-α,and airway remodeling indicators,along with mRNA levels of HMGB1,TLR4,and NF-κB p65 and protein levels of HMGB1,TLR4,and p-NF-κB p65,were all reduced(P<0.05)in a dose-dependent manner.When compared to the dexamethasone group,the low and medium dose iris xanthin groups showed decreases in LV and VE(P<0.05),whereas Penh values,IL-1β,IL-6,TNF-α,and airway remodeling indicators,along with mRNA levels of HMGB1,TLR4,NF-κB p65 and protein levels of HMGB1,TLR4,and p-NF-κB p65,were increased(P<0.05).No significant differences were noted in these indices between the high dose iris xan

关 键 词：鸢尾黄素 哮喘 气道炎症 气道重塑 HMGB1/TLR4/NF-κB通路 幼鼠 

分 类 号：R285.5[医药卫生—中药学]