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川芎嗪通过AMPK/NF-κB和Nrf-2/HO-1途径减轻过敏性气道炎症和氧化应激的实验研究
引用本文:徐畅,宋艺兰,姜京植,王知广,朴艺花,李良昌,延光海.川芎嗪通过AMPK/NF-κB和Nrf-2/HO-1途径减轻过敏性气道炎症和氧化应激的实验研究[J].免疫学杂志,2021(2):100-106.
作者姓名:徐畅  宋艺兰  姜京植  王知广  朴艺花  李良昌  延光海
作者单位:吉林省过敏性常见疾病免疫与靶向研究重点实验室;延边大学医学院解剖教研室;延边大学附属医院呼吸内科;延边大学附属医院重症医学科
基金项目:国家自然科学基金(81970018,81860729)。
摘    要:目的本研究旨在探讨川芎嗪对过敏性炎症反应和氧化应激的影响,并探讨其机制是否与AMPK/NF-κB和Nrf-2/HO-1信号通路有关。方法用组织化学染色来观察小鼠肺组织病理学改变;小鼠支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中炎症细胞数量用Diff-quik染色法检测;用ELISA法检测BALF中各种细胞因子和IgE的含量以及SOD,CAT活性和MDA表达水平;免疫荧光法检测p-AMPK和NF-κBp65在肺组织中表达水平;免疫组化法检测Nrf-2和HO-1在肺组织中表达水平;肺中的AMPK、p-AMPK、NF-κBp65、Nrf-2和HO-1蛋白进行定量分析采用Westernblot方法。结果哮喘小鼠模型中,川芎嗪可减少炎症细胞的渗出和浸润,抑制杯状细胞增生。川芎嗪治疗后,哮喘小鼠BALF中白细胞介素4(IL-4)、IL-5、IL-13和IgE等蛋白表达水平明显降低,而干扰素-γ(IFN-γ)的表达增高。川芎嗪治疗后可使哮喘小鼠BALF中SOD和CAT活性升高,而MDA表达水平降低。川芎嗪也可降低OVA诱导哮喘小鼠NF-κBp65的表达,增加p-AMPK、Nrf-2和HO-1的表达。结论川芎嗪可以改善哮喘小鼠气道炎症反应和氧化应激,其机制可能与AMPK/NF-κB和Nrf-2/HO-1信号通路有关。

关 键 词:哮喘  川芎嗪  AMPK/NF-κB信号通路  Nrf-2/HO-1信号通路  氧化应激

Ligustrazine reduces allergic airway inflammation and oxidative stress through AMPK/NF-κB and Nrf-2/HO-1 pathways
XU Chang,SONG Yilan,JIANG Jingzhi,WANG Zhiguang,PIAO Yihua,LI Liangchang,YAN Guanghai.Ligustrazine reduces allergic airway inflammation and oxidative stress through AMPK/NF-κB and Nrf-2/HO-1 pathways[J].Immunological Journal,2021(2):100-106.
Authors:XU Chang  SONG Yilan  JIANG Jingzhi  WANG Zhiguang  PIAO Yihua  LI Liangchang  YAN Guanghai
Institution:(Key Laboratory of Immunization and Targeting of Common Allergic Diseases in Jilin Province,Yanji 133002,China;Department of Anatomy,College of Medicine,Yanbian University,Yanji 133002,China;Department of Respiratory,Yanbian UniversityHospital,Yanji 133002,China;Department of Critical Care Medicine,Yanbian University Hospital,Yanji 133000,China)
Abstract:This study was designed to investigate the effect of ligustrazine on allergic inflammation and oxidative stress,and the roles of AMPK/NF-κB and Nrf-2/HO-1 signaling pathways in the processes.The pathological changes of lung tissue were observed by histochemical staining;the number of inflammatory cells in BALF was counted by Diff-quik staining;the contents of cytokines and IgE in bronchoalveolar lavage fluid(BALF),the activities of SOD,CAT and the expression of MDA in BALF were detected by ELISA.The expression of pAMPK and NF-κBp65 in lung tissue were detected by immunofluorescence;the expression levels of Nrf-2 and HO-1 in lung tissue were detected by immunohistochemistry.Western blot was used to analyze the levels AMPK,pAMPK,NF-κBp65,Nrf-2 and HO-1 in lung tissue.Data showed in ovalbum(OVA)-induced asthma mice model,ligustrazine could reduce the infiltration of inflammatory cells and inhibit the proliferation of goblet cells.After treatment with ligustrazine,the expression levels of IL-4,IL-5,IL-13 and IgE in BALF of asthmatic mice were significantly decreased,but the expression of IFN-γwas increased.Ligustrazine could also increase the levels of SOD and CAT,but decrease the level of MDA in BALF.Ligustrazine could decrease the expression of NF-κBp65 and increase the expression levels of p-AMPK,Nrf-2 and HO-1 in OVA-induced asthmatic mice.Taken together,ligustrazine can alleviate airway inflammation and oxidative stress in asthmatic mice,and the mechanism may be related to AMPK/NF-κB and Nrf-2/HO-1 signaling pathways.
Keywords:Asthma  Ligustrazine  AMPK/NF-κBsignaling pathway  Nrf-2/HO-1signaling pathway  Oxidative stress
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