小儿清炎合剂通过Nrf2/HO-1信号通路减轻哮喘小鼠气道炎症  

Xiaoer Qingyan Mixture Attenuates Airway Inflammation in Asthmatic Mice Through Regulation of NF-κB and Nrf2/HO-1 Signaling Pathways

作　　者：朱慧婷[1] 易鹏飞[1] 万慕湲[1] 刘建明 ZHU Huiting;YI Pengfei;WAN Muyuan;LIU Jianming(Department of Pharmacy,Jiangxi Provincial Children's Hospital,Nanchang 330006,China;Department of Pharmacy,The First Affiliated Hospital of Nanchang University,Nanchang 330006,China)

机构地区：[1]江西省儿童医院药学部,南昌330006 [2]南昌大学第一附属医院药学部,南昌330006

出　　处：《江西中医药大学学报》2024年第4期84-88,共5页Journal of Jiangxi University of Chinese Medicine

基　　金：江西省中医药管理局科技计划项目(2021B628)。

摘　　要：目的:探讨小儿清炎合剂(XQM)对哮喘模型小鼠气道炎症的影响及其分子机制。方法:将36只SPF级雄性BALB/c小鼠随机分为6组(n=6),即正常对照组、哮喘模型组、孟鲁司特纳(阳性药)组及XQM低、中、高剂量组(10、20、40 mg/kg);通过腹腔注射卵清蛋白(OVA)和雾化激发构建哮喘小鼠模型;使用肺功能测定仪测定小鼠肺功能;采用HE染色考察小鼠肺组织病理变化;ELISA测定肺泡灌洗液中相关细胞因子水平;采用试剂盒测定小鼠肺组织中氧化应激相关因子水平;RT-qPCR和Western blot检测小鼠肺组织中核因子E2相关因子2(Nrf2)及血红素氧合酶1(HO-1)的基因表达变化。结果:与正常对照组比较,哮喘模型组小鼠的肺阻力增加而动态顺应性下降(P<0.05),肺组织病理炎性改变明显,肺泡灌洗液IL-5、IL-13和TNF-α水平均提高,而INF-γ表达水平较低(P<0.05),活性氧和丙二醛含量升高,而总抗氧化能力、超氧化物歧化酶活性、过氧化氢酶和谷胱甘肽过氧化物酶水平降低(P<0.05);XQM处理可显著减少上述变化,且表现为剂量依赖性,XQM可上调Nrf2和HO-1的mRNA水平,并且可促进Nrf2核蛋白和HO-1总蛋白表达。结论:XQM对OVA诱导的哮喘模型小鼠气道具有保护作用,该作用机制可能与Nrf2/HO-1通路的激活有关。Objective:To investigate the effects of Xiaoer Qingyan Mixture(XQM)on airway inflammation in asthmatic mice and its molecular mechanism.Methods:36 SPF grade male BALB/c mice were randomly divided into 6 groups(n=6),namely normal control group,asthma model group,Montelukhtna(positive drug)group and XQM low,medium and high dose(10,20,40 mg/kg)group.A mouse model of asthma was constructed by intraperitoneal injection of ovalbumin(OVA)and atomization stimulation.The lung function of mice was measured by pulmonary function meter.HE staining was used to investigate the pathological changes of lung tissue.The levels of related cytokines in alveolar lavage fluid were determined by ELISA.The levels of oxidative stress related factors in mouse lung tissues were determined by a kit.The gene expression of nuclear factor E2-related factor 2(Nrf2)and heme oxygenase 1(HO-1)in mouse lung was detected by RT-qPCR and Western blot.Results:Compared with the normal control group,the pulmonary resistance(RL)was increased and the dynamic compliance(Cdyn)was decreased(P<0.05),the pathological inflammatory changes of lung tissue were obvious,the levels of IL-5,IL-13 and TNF-αwere increased in alveolar lavage fluid,and the expression level of INF-γwas lower(P<0.05).The contents of reactive oxygen species(ROS)and malondialdehyde(MDA)were increased,but the levels of total antioxidant capacity(T-AOC),superoxide dismutase(SOD)activity,catalase(CAT)and glutathione peroxidase(GSH-Px)were decreased(P<0.05).XQM treatment can significantly reduce the above changes in a dose-dependent manner.XQM can up-regulate the mRNA levels of Nrf2 and HO-1,and promote the expression of Nrf2 nuclear protein and HO-1 protein.Conclusion:XQM has protective effect on the airway of OVA-induced asthmatic mice,and the mechanism may be related to the activation of Nrf2/HO-1 pathway.

关 键 词：小儿清炎合剂 哮喘 核因子E2相关因子2 血红素氧合酶1 炎症 

分 类 号：R285[医药卫生—中药学]