Zhu Dongwei, Zhao Qi, Pan Tingyu, Bai Le, Zhao Yisheng, Wang Jing, Wang Zhichao, Xu Yong, Zhou Xianmei
Department of Respiratory and Critical Care Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Phytomedicine. 2025 Sep;145:157041. doi: 10.1016/j.phymed.2025.157041. Epub 2025 Jul 5.
Pulmonary fibrosis (PF) is a progressive and irreversible pathological manifestation of fibrotic interstitial lung diseases, characterized by chronic inflammation, excessive extracellular matrix (ECM) deposition, and architectural distortion of lung parenchyma, ultimately leading to respiratory failure. Maiwei Yangfei Decoction (MWYF) has been clinically applied in PF treatment, and can effectively improve the lung function and life quality of PF patients. Nevertheless, the precise regulatory mechanisms underlying its anti-fibrotic effects require further investigation.
To investigate MWYF's pharmacological action and potential mechanism against PF.
Firstly, a PF mouse model was established by intratracheal nebulization of bleomycin (BLM). The effect of MWYF on PF was evaluated through micro-CT imaging and histopathological analysis. Subsequently, transcriptomics and proteomics were employed to investigate the crucial mechanism underlying the anti-fibrotic effects of MWYF. Immunofluorescence (IF), ELISA, TEM, SEM, Western blot (WB), and qPCR were then conducted to validate the inhibitory effects of MWYF on alveolar macrophages (AM) pyroptosis both in vivo and in vitro. Finally, the NLRP3 inhibitor (MCC950) was applied in MH-S cells to investigate the impact of MWYF on NLRP3 inflammasome.
MWYF exhibited significant efficacy against BLM-induced PF. Integrated transcriptomic and proteomic analyses suggested that NLRP3 inflammasome-mediated pyroptosis intrinsically participated in the anti-fibrotic effects of MWYF. Further in-vivo experiments confirmed that MWYF alleviated AM pyroptosis in lung tissues via modulating the assembly of the NLRP3 inflammasome. In vitro, MWYF inhibited LPS plus Nigericin-induced pyroptosis in MH-S cells, as well as primary mouse lung fibroblast (PMLF) proliferation, activation, and ECM secretion, by suppressing NLRP3 inflammasome activation.
This study illustrated that MWYF alleviated PF by inhibiting NLRP3 inflammasome-mediated AM pyroptosis by integrating multi-omics approaches, indicating that MWYF had promising clinical translational potential in PF therapy.
肺纤维化（PF）是纤维化间质性肺疾病的一种进行性且不可逆的病理表现，其特征为慢性炎症、细胞外基质（ECM）过度沉积以及肺实质结构扭曲，最终导致呼吸衰竭。麦味养肺汤（MWYF）已在PF治疗中临床应用，且能有效改善PF患者的肺功能和生活质量。然而，其抗纤维化作用的确切调控机制仍需进一步研究。
探讨MWYF对PF的药理作用及潜在机制。
首先，通过气管内雾化博来霉素（BLM）建立PF小鼠模型。通过微型计算机断层扫描（micro-CT）成像和组织病理学分析评估MWYF对PF的影响。随后，采用转录组学和蛋白质组学研究MWYF抗纤维化作用的关键机制。接着进行免疫荧光（IF）、酶联免疫吸附测定（ELISA）、透射电子显微镜（TEM）、扫描电子显微镜（SEM）、蛋白质免疫印迹法（WB）和定量聚合酶链反应（qPCR），以验证MWYF在体内和体外对肺泡巨噬细胞（AM）焦亡的抑制作用。最后，将NLRP3抑制剂（MCC950）应用于小鼠肺泡巨噬细胞系（MH-S）细胞，以研究MWYF对NLRP3炎性小体的影响。
MWYF对BLM诱导的PF显示出显著疗效。综合转录组学和蛋白质组学分析表明，NLRP3炎性小体介导的焦亡内在地参与了MWYF的抗纤维化作用。进一步的体内实验证实，MWYF通过调节NLRP3炎性小体的组装减轻肺组织中的AM焦亡。在体外，MWYF通过抑制NLRP3炎性小体激活，抑制脂多糖（LPS）加尼日利亚菌素诱导的MH-S细胞焦亡以及原代小鼠肺成纤维细胞（PMLF）的增殖、激活和ECM分泌。
本研究表明，MWYF通过整合多组学方法抑制NLRP3炎性小体介导的AM焦亡来减轻PF，表明MWYF在PF治疗中具有良好的临床转化潜力。
