Chen Si, Piao Ying, Song Yilan, Wang Zhiguang, Jiang Jingzhi, Piao Yihua, Li Li, Xu Chang, Li Liangchang, Chi Yongxue, Jin Guihua, Yan Guanghai
Department of Pediatrics, Affiliated Hospital of Yanbian University, Yanji 133099, Jilin, P. R. China.
Department of Neonatology, Children's Hospital of Changchun, Changchun 130061, Jilin, P. R. China.
Open Med (Wars). 2022 Jul 7;17(1):1158-1171. doi: 10.1515/med-2022-0513. eCollection 2022.
The aim of this study is to investigate the protective effects of glaucocalyxin A (GLA) on airways in mouse models of asthma, concerning the inflammatory mediators, Th1/Th2 subgroup imbalance, and Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Hematoxylin and eosin/periodic acid-Schiff staining was used to observe the pathological changes in lung tissues. Inflammatory cytokine contents in the bronchoalveolar lavage fluid were detected by enzyme-linked immunosorbent assay. Protein expression levels were detected with Western blot, immunohistochemistry, and immunofluorescence. studies showed that, in ovalbumin (OVA)-induced asthmatic mouse models, the GLA treatments reduced the airway hyperresponsiveness and the secretion of inflammatory cells, declined the proliferation of goblet cells, decreased the levels of IL-4, IL-5, and IL-13, and increased the contents of interferon-γ and IL-12. Moreover, GLA inhibited the protein expression levels of TLR4, MyD88, TRAF6, and NF-κB in OVA-induced asthmatic mouse models. Further studies showed that GLA inhibited the expression of NF-κB, p-IκBα, tumor necrosis factor-α, IL-6, and IL-1β and blocked the nuclear transfer of NF-κB in lipopolysaccharide-stimulated RAW264.7 macrophages. Conclusively, GLA can inhibit the inflammatory responses in OVA-induced asthmatic mice and inhibit the release of inflammatory factors in LPS-induced RAW264.7 macrophages, which may be related to the inhibition of TLR4/NF-κB signaling pathway.
本研究旨在探讨青兰素A（GLA）对哮喘小鼠模型气道的保护作用，涉及炎症介质、Th1/Th2亚群失衡以及Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路。采用苏木精-伊红/过碘酸-希夫染色观察肺组织的病理变化。通过酶联免疫吸附测定法检测支气管肺泡灌洗液中炎症细胞因子的含量。用蛋白质免疫印迹法、免疫组织化学法和免疫荧光法检测蛋白表达水平。研究表明，在卵清蛋白（OVA）诱导的哮喘小鼠模型中，GLA处理可降低气道高反应性和炎症细胞分泌，减少杯状细胞增殖，降低白细胞介素-4、白细胞介素-5和白细胞介素-13水平，并增加干扰素-γ和白细胞介素-12的含量。此外，GLA可抑制OVA诱导的哮喘小鼠模型中TLR4、髓样分化因子88（MyD88）、肿瘤坏死因子受体相关因子6（TRAF6）和NF-κB的蛋白表达水平。进一步研究表明，GLA可抑制脂多糖刺激的RAW264.7巨噬细胞中NF-κB、磷酸化核因子κB抑制蛋白α（p-IκBα）、肿瘤坏死因子-α、白细胞介素-6和白细胞介素-1β的表达，并阻断NF-κB的核转位。综上所述，GLA可抑制OVA诱导的哮喘小鼠的炎症反应，并抑制脂多糖诱导的RAW264.7巨噬细胞中炎症因子的释放，这可能与抑制TLR4/NF-κB信号通路有关。
