止喘灵通过 PI3K/AKT/mTOR/STAT6 通路抑制 M2 型巨噬细胞极化缓解 OVA 诱导的过敏反应
2026/03/05
摘要
背景：过敏性哮喘主要由 Th2 型免疫反应介导，是一种严重威胁人类健康的慢性呼吸系统疾病。止喘灵（ZCL）是临床上广泛用于治疗哮喘与喘息性支气管炎的中药，已被证实可缓解气道痉挛、抑制气道炎症，但其调控巨噬细胞极化这一关键 Th2 型炎症过程的机制尚不明确。
目的：本研究旨在评价止喘灵对过敏性哮喘的治疗作用，并探讨其调控巨噬细胞极化的分子机制。
方法：采用高效液相色谱法（HPLC）分析止喘灵的化学成分；建立卵清蛋白（OVA）诱导的过敏性哮喘小鼠模型，评价止喘灵的抗哮喘作用。机制研究包括苏木精 伊红（H&E）染色、马松三色（MT）染色、免疫荧光（IF）、酶联免疫吸附试验（ELISA）、流式细胞术（FCM）、转录组测序、蛋白免疫印迹（WB），以及计算机分子对接，用于预测止喘灵主要成分与参与 M2 型巨噬细胞极化及气道炎症的靶蛋白的结合作用。
结果：在体内实验中，止喘灵可显著改善哮喘症状、减轻气道炎症。机制上，止喘灵通过调控 PI3K/AKT/mTOR/STAT6 信号通路抑制 M2 型巨噬细胞极化。分子对接结果显示，止喘灵主要成分与 PI3K、AKT、mTOR、STAT6 均具有良好的结合能力，提示其可能通过调控这些信号分子发挥作用。
结论：止喘灵通过 PI3K/AKT/mTOR/STAT6 通路抑制 M2 型巨噬细胞极化，并与通路关键蛋白直接结合，从而减轻气道炎症与重塑，发挥抗过敏性哮喘作用。本研究为止喘灵治疗过敏性哮喘提供了功能与分子层面的实验依据。
Zhi-Chuan-Ling alleviates OVA-induced allergic asthma by suppressing M2 macrophage polarization via the PI3K/AKT/mTOR/STAT6 pathway.
Xing S, Chen H, Wang L, Lv S, Zhu J, Wang Z, Han J, Zhang H, Fang R, Wu J, Shao F, Han J, Sun L.
Abstract
BACKGROUND:Allergic asthma, predominantly driven by Th2 immune responses, is a chronic respiratory disease that poses a significant threat to human health. Zhi-Chuan-Ling (ZCL), a traditional Chinese medicine widely used for the treatment of asthma and wheezy bronchitis, has been shown to relieve airway constriction and suppress airway inflammation. However, its mechanisms in regulating macrophage polarization, a key Th2-driven inflammatory process, remain unclear.
OBJECTIVES:This study aimed to assess the therapeutic effects of ZCL on allergic asthma and to investigate its molecular mechanisms in modulating macrophage polarization.
METHODS:The chemical profile of ZCL was characterized by high-performance liquid chromatography (HPLC). An ovalbumin (OVA)-induced mouse model of allergic asthma was established to assess the anti-asthmatic effects of ZCL. Mechanistic studies included hematoxylin-eosin (H&E) and Masson's trichrome (MT) staining, immunofluorescence (IF), ELISA, flow cytometry (FCM), transcriptomic profiling, Western blotting (WB), and in silico molecular docking to predict binding interactions of key ZCL compounds with target proteins involved in M2 macrophage polarization and airway inflammation.
RESULTS:ZCL treatment significantly alleviated asthma symptoms and reduced airway inflammation in vivo. Mechanistically, ZCL inhibited M2 macrophage polarization by modulating the PI3K/AKT/mTOR/STAT6 signaling pathway. Molecular docking analysis revealed favorable binding of major ZCL compounds to PI3K, AKT, mTOR, and STAT6, supporting their potential role in modulating these signaling molecules.
CONCLUSIONS:ZCL protects against allergic asthma by suppressing M2 macrophage polarization through the PI3K/AKT/mTOR/STAT6 axis and by directly interacting with key pathway proteins, thereby attenuating airway inflammation and remodeling. These findings provide both functional and molecular evidence for the therapeutic potential of ZCL in allergic asthma.
背景：过敏性哮喘主要由 Th2 型免疫反应介导，是一种严重威胁人类健康的慢性呼吸系统疾病。止喘灵（ZCL）是临床上广泛用于治疗哮喘与喘息性支气管炎的中药，已被证实可缓解气道痉挛、抑制气道炎症，但其调控巨噬细胞极化这一关键 Th2 型炎症过程的机制尚不明确。
目的：本研究旨在评价止喘灵对过敏性哮喘的治疗作用，并探讨其调控巨噬细胞极化的分子机制。
方法：采用高效液相色谱法（HPLC）分析止喘灵的化学成分；建立卵清蛋白（OVA）诱导的过敏性哮喘小鼠模型，评价止喘灵的抗哮喘作用。机制研究包括苏木精 伊红（H&E）染色、马松三色（MT）染色、免疫荧光（IF）、酶联免疫吸附试验（ELISA）、流式细胞术（FCM）、转录组测序、蛋白免疫印迹（WB），以及计算机分子对接，用于预测止喘灵主要成分与参与 M2 型巨噬细胞极化及气道炎症的靶蛋白的结合作用。
结果：在体内实验中，止喘灵可显著改善哮喘症状、减轻气道炎症。机制上，止喘灵通过调控 PI3K/AKT/mTOR/STAT6 信号通路抑制 M2 型巨噬细胞极化。分子对接结果显示，止喘灵主要成分与 PI3K、AKT、mTOR、STAT6 均具有良好的结合能力，提示其可能通过调控这些信号分子发挥作用。
结论：止喘灵通过 PI3K/AKT/mTOR/STAT6 通路抑制 M2 型巨噬细胞极化，并与通路关键蛋白直接结合，从而减轻气道炎症与重塑，发挥抗过敏性哮喘作用。本研究为止喘灵治疗过敏性哮喘提供了功能与分子层面的实验依据。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（Phytomedicine. 2026 Feb 1;153:157911. doi: 10.1016/j.phymed.2026.157911. Epub ahead of print. PMID: 41650521.）
（Phytomedicine. 2026 Feb 1;153:157911. doi: 10.1016/j.phymed.2026.157911. Epub ahead of print. PMID: 41650521.）
Zhi-Chuan-Ling alleviates OVA-induced allergic asthma by suppressing M2 macrophage polarization via the PI3K/AKT/mTOR/STAT6 pathway.
Xing S, Chen H, Wang L, Lv S, Zhu J, Wang Z, Han J, Zhang H, Fang R, Wu J, Shao F, Han J, Sun L.
Abstract
BACKGROUND:Allergic asthma, predominantly driven by Th2 immune responses, is a chronic respiratory disease that poses a significant threat to human health. Zhi-Chuan-Ling (ZCL), a traditional Chinese medicine widely used for the treatment of asthma and wheezy bronchitis, has been shown to relieve airway constriction and suppress airway inflammation. However, its mechanisms in regulating macrophage polarization, a key Th2-driven inflammatory process, remain unclear.
OBJECTIVES:This study aimed to assess the therapeutic effects of ZCL on allergic asthma and to investigate its molecular mechanisms in modulating macrophage polarization.
METHODS:The chemical profile of ZCL was characterized by high-performance liquid chromatography (HPLC). An ovalbumin (OVA)-induced mouse model of allergic asthma was established to assess the anti-asthmatic effects of ZCL. Mechanistic studies included hematoxylin-eosin (H&E) and Masson's trichrome (MT) staining, immunofluorescence (IF), ELISA, flow cytometry (FCM), transcriptomic profiling, Western blotting (WB), and in silico molecular docking to predict binding interactions of key ZCL compounds with target proteins involved in M2 macrophage polarization and airway inflammation.
RESULTS:ZCL treatment significantly alleviated asthma symptoms and reduced airway inflammation in vivo. Mechanistically, ZCL inhibited M2 macrophage polarization by modulating the PI3K/AKT/mTOR/STAT6 signaling pathway. Molecular docking analysis revealed favorable binding of major ZCL compounds to PI3K, AKT, mTOR, and STAT6, supporting their potential role in modulating these signaling molecules.
CONCLUSIONS:ZCL protects against allergic asthma by suppressing M2 macrophage polarization through the PI3K/AKT/mTOR/STAT6 axis and by directly interacting with key pathway proteins, thereby attenuating airway inflammation and remodeling. These findings provide both functional and molecular evidence for the therapeutic potential of ZCL in allergic asthma.
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