Tian Yange, Song Qinghua, Lu Ruilong, Du Yan, Qiu Zhiguang, Liao Yixi, Wang Bo, Li Jiansheng
Henan University of Chinese Medicine, 156 Jinshui East Road, Jinshui District, Zhengzhou, 450046, Henan Province, China.
Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed By Henan Province & Education Ministry of P.R. China, Zhengzhou, 450046, China.
Chin Med. 2025 Aug 20;20(1):129. doi: 10.1186/s13020-025-01184-0.
Idiopathic Pulmonary fibrosis (IPF) is a progressive lung disease with poor survival. Electroacupuncture has been proven to improve dyspnea in IPF patients, but the mechanism remains unclear.
The IPF rat model was established by intratracheal instillation of bleomycin. Electroacupuncture was performed 3 times a week for 4 weeks. Lung function and lung histopathology were tested to evaluate the respiratory movements and lung damage. Collagen I (COL-I), α-smooth muscle actin (α-SMA) and hydroxyproline (HYP) were measured to evaluate fiber deposition. Characterization of gene and protein expression profiles in IPF rat was recognized by integrated proteomic and transcriptomic. WGCNA and GSEA were used to identify the key modules and signaling pathways of electroacupuncture against IPF.
Electroacupuncture improved vital capacity, RI, Cdyn, the alveolar rupture and fibrous tissue deposition, and reduced the expression of α-SMA, COL-I, and HYP. 1104 differentially expressed genes and 391 proteins were identified which were reversed by electroacupuncture. Two modules were obtained and functional analysis showed ferroptosis, PI3K-AKT and FoxO signaling pathway were significantly enriched. Genes and proteins with strong correlations were screened out, and functional analysis showed ferroptosis and glutathione metabolism were significantly enriched. Electroacupuncture reduced the levels of Fe, Fe, LPO and MDA in the lung tissue of PF rats and increased the levels of GSH and SOD. Further, electroacupuncture improved the mitochondrial swelling of alveolar epithelial cells in PF rats. Also, electroacupuncture inhibited the level of p-Akt and p-FoxO3.
Electroacupuncture regulated ferroptosis to improve IPF via inhibiting PI3K-AKT and FoxO signaling.
特发性肺纤维化(IPF)是一种预后较差的进行性肺部疾病。电针已被证明可改善IPF患者的呼吸困难,但其机制尚不清楚。
通过气管内注入博来霉素建立IPF大鼠模型。每周进行3次电针治疗,共4周。检测肺功能和肺组织病理学以评估呼吸运动和肺损伤。测量I型胶原蛋白(COL-I)、α平滑肌肌动蛋白(α-SMA)和羟脯氨酸(HYP)以评估纤维沉积。通过蛋白质组学和转录组学整合识别IPF大鼠的基因和蛋白质表达谱特征。采用加权基因共表达网络分析(WGCNA)和基因集富集分析(GSEA)来确定电针对IPF的关键模块和信号通路。
电针改善了肺活量、RI、Cdyn、肺泡破裂和纤维组织沉积,并降低了α-SMA、COL-I和HYP的表达。鉴定出1104个差异表达基因和391种蛋白质,电针可使其逆转。获得了两个模块,功能分析表明铁死亡、PI3K-AKT和FoxO信号通路显著富集。筛选出具有强相关性的基因和蛋白质,功能分析表明铁死亡和谷胱甘肽代谢显著富集。电针降低了PF大鼠肺组织中Fe²⁺、Fe³⁺、脂质过氧化物(LPO)和丙二醛(MDA)的水平,提高了谷胱甘肽(GSH)和超氧化物歧化酶(SOD)的水平。此外,电针改善了PF大鼠肺泡上皮细胞的线粒体肿胀。同时,电针抑制了p-Akt和p-FoxO3的水平。
电针通过抑制PI3K-AKT和FoxO信号通路调节铁死亡以改善IPF。