射干麻黄汤通过抑制CCL3介导的NETosis改善肺纤维化进展
Shegan Mahuang Decoction ameliorates pulmonary fibrosis progression by inhibiting CCL3-mediated NETosis.
摘要(中文译文)
肺纤维化（PF）代表一系列慢性肺部疾病，其有效的治疗选择仍然有限。射干麻黄汤（SGMH）是一种对呼吸系统疾病具有潜在治疗作用的中药。SGMH治疗PF的确切机制尚未阐明。本研究旨在探讨SGMH治疗PF的有效性及机制。为研究SGMH对PF的作用，我们建立了小鼠模型并评估了炎症及中性粒细胞胞外诱捕网（NETs）相关标志物。通过整合多组学分析筛选SGMH的靶基因。通过一系列实验探讨SGMH的机制，包括使用DNase I清除NETs、Pad4小鼠模型以及通过腹腔注射重组CCL3（rCCL3）或CCL3中和抗体（anti-CCL3）进行药物调控。SGMH改善了博来霉素诱导的肺组织损伤，还抑制了肺部炎症和NETs形成。DNase I介导的NETs清除和Pad4小鼠模型均表明SGMH不能进一步改善PF，提示SGMH通过抑制NETs形成来阻断PF的发展。多组学分析和实验验证发现SGMH通过靶向CCL3抑制NETs形成。给予rCCL3可恢复NETs形成并减弱SGMH的抗纤维化作用。此外，单独使用anti-CCL3治疗可抑制PF，而与其与SGMH联合使用并未进一步增强治疗效果。本研究表明SGMH通过抑制CCL3介导的NETosis改善PF进展，提示其作为PF治疗的潜在临床应用价值。
Abstract
Pulmonary fibrosis (PF) represents a spectrum of chronic lung disorders for which effective therapeutic options remain limited. Shegan Mahuang Decoction (SGMH) is a traditional Chinese medicine with potential therapeutic effects for respiratory system diseases. The precise mechanism of SGMH in treating PF has not yet been elucidated. This study aims to investigate the effectiveness and mechanism of SGMH in the treatment of PF. To investigate the effect of SGMH on PF, we established a mouse model and assessed inflammatory and neutrophil extracellular traps (NETs)-related markers. The target gene of SGMH was screened through integrated multi-omics analysis. The mechanisms of SGMH were explored through a series of experiments, encompassing NETs depletion with DNase I, the Pad4 mouse model, and pharmacological modulation via intraperitoneal administration of recombinant CCL3 (rCCL3) or a CCL3 neutralizing antibody (anti-CCL3). SGMH ameliorated Bleomycin-induced lung tissue damage. It also inhibited pulmonary inflammation and NETs formation. Both DNase I-mediated NETs clearance and the Pad4 mice model showed that SGMH could not further ameliorate PF, indicating that SGMH blocks the PF development by inhibiting NETs formation. Multi-omics analysis and experimental validation found that SGMH inhibits NETs formation by targeting CCL3. Administration of rCCL3 restored NETs formation and attenuated the anti-fibrotic effect of SGMH. Moreover, treatment with anti-CCL3 alone inhibited PF, whereas its combination with SGMH did not further enhance the therapeutic effect. This study demonstrated that SGMH ameliorates PF progression by inhibiting CCL3-mediated NETosis, suggesting its potential clinical application for PF treatment.
如何引用
AMA
Wencheng Zhou, Zhisen Wang, Haojie Du, Wanjun Zhao, Tao Zhang, Zhengcheng Liu, et al. Shegan Mahuang Decoction ameliorates pulmonary fibrosis progression by inhibiting CCL3-mediated NETosis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158386.
APA
Wencheng Zhou, Zhisen Wang, Haojie Du, Wanjun Zhao, Tao Zhang, Zhengcheng Liu, et al (2026). Shegan Mahuang Decoction ameliorates pulmonary fibrosis progression by inhibiting CCL3-mediated NETosis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158386
GB/T 7714
Wencheng Zhou, Zhisen Wang, Haojie Du, Wanjun Zhao, Tao Zhang, Zhengcheng Liu, et al. Shegan Mahuang Decoction ameliorates pulmonary fibrosis progression by inhibiting CCL3-mediated NETosis.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158386.
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