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目的 基于Janus激酶2/信号转导及转录激活因子3(JAK2/STAT3)信号通路探讨黄芪甲苷（Ast）抑制肺成纤维细胞转分化为肌成纤维细胞改善小鼠特发性肺纤维化（IPF）的作用机制。方法 将24只C57BL/6小鼠随机分为模型组、Ast组、Ast+Colivelin(JAK2激动剂)组，采用第1、7、14天予以气管滴注博来霉素（4 mg/kg）构建IPF小鼠模型，造模完成后，各组小鼠给予相应药物干预，连续给药21 d。另取8只同龄小鼠作为对照组。苏木素-伊红（HE）染色观察肺组织病理变化；马松（Masson）染色观察肺组织纤维化情况；ELISA检测肺泡灌洗液（BALF）中炎症因子IL-6、IL-1β、TNF-α的表达水平；试剂盒检测肺组织中羟脯氨酸（HYP）的表达水平；免疫组织化学染色检测各组肺组织中α-平滑肌肌动蛋白（α-SMA）、胶原蛋白Ⅰ(Collagen Ⅰ)及转化生长因子-β1(TGF-β1)蛋白的表达水平；Western Blot检测肺组织中JAK2、STAT3、p-JAK2及p-STAT3蛋白表达水平。结果 Ast干预后肺组织病理损伤与纤维化明显减轻，IL-6、IL-1β、TNF-α、HYP表达水平显著降低（P<0.05），肺组织中α-SMA、Collagen Ⅰ、TGF-β1表达水平显著降低（P<0.05）,p-JAK2/JAK2、p-STAT3/STAT3比例显著降低（P<0.05）；而Colivelin能部分逆转Ast对上述指标的调控作用。结论 Ast可有效缓解IPF小鼠的炎症反应，抑制肺成纤维细胞的转分化过程，进而减轻小鼠IPF程度，其作用机制可能与抑制JAK2/STAT3信号通路有关。
Abstract：Objective To investigate the mechanism by which astragaloside Ⅳ(Ast) inhibits the transdifferentiation of fibroblasts into myofibroblasts and ameliorates idiopathic pulmonary fibrosis(IPF) in mice, focusing on the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway. Methods 24 C57 BL/6 mice were randomly assigned to three groups: the model group, the Ast group, and the Ast + Colivelin(JAK2 agonist) group. The IPF mouse model was induced through tracheal instillation of bleomycin(4 mg/kg) on days 1, 7 and 14. Following model establishment, each group received the corresponding drug intervention for 21 consecutive days. An additional eight age-matched mice served as the control group. Pathological alterations in lung tissue were assessed using hematoxylin-eosin(HE) staining, and Masson staining was utilized to evaluate lung tissue fibrosis. The levels of inflammatory factors, including IL-6, IL-1β and TNF-α, in bronchoalveolar lavage fluid(BALF) were measured via ELISA. Hydroxyproline(HYP) levels in lung tissue were quantified using a specific kit. To assess the expression of α-SMA, Collagen I and TGF-β1, immunohistochemical staining techniques were employed. Furthermore, protein expression levels of JAK2, STAT3, p-JAK2 and p-STAT3 in lung tissue were evaluated through Western Blot. Results Following Ast intervention, pathological injury and fibrosis in lung tissue were significantly alleviated. The expression levels of IL-6, IL-1β, TNF-α and HYP were markedly reduced(P<0.05), while the expression levels of α-SMA, Collagen Ⅰ and TGF-β1 in lung tissue also significantly decreased(P<0.05). The ratios of p-JAK2/JAK2 and p-STAT3/STAT3 exhibited significant reductions(P<0.05); however, Colivelin partially reversed the regulatory effects of Ast on these indicators. Conclusion Ast can effectively reduce the inflammatory response in mice suffering from IPF, inhibit the transdifferentiation of lung fibroblasts, and consequently diminish the severity of IPF in these subjects. The underlying mechanism of action is likely associated with the suppression of the JAK2/STAT3 signaling pathway.
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基本信息:
DOI：10.13728/j.1673-6427.2026.01.004
中图分类号:R285.5
引用信息:
[1]郭晓菲,刘震,商艳,等.黄芪甲苷抑制肺成纤维细胞转分化减轻小鼠特发性肺纤维化的作用机制研究[J].现代中药研究与实践,2026,40(01):24-30.DOI:10.13728/j.1673-6427.2026.01.004.
基金信息:
大连大学学科交叉项目（DLUXK-2023-YB-006）