Treatise·ZHUOYUE
YAN Yanan, FANG Fang, WANG Hao, HAO Ruiwen, LI Wei, TANG Yuwei, WANG Jiepeng, FANG Chaoyi
China Journal of Traditional Chinese Medicine and Pharmacy.
2025, 40(5):
2144-2150.
Objective: To observe the changes of lung function in rats with idiopathic pulmonary fibrosis (IPF) under the regulation of iron autophagy-ferroptosis pathway by Shengxian Decoction, and revealing the scientific significance of IPF under the guidance of the ‘Da qi theory’. Methods: Forty-eight SPF rats were randomly divided into Sham group, Model group, Nintedanib group, and Shengxian Decoction group. Intratracheal drip Bleomycin (5 mg/kg) was used in order to prepare a rat model of IPF. Starting from the next day of modeling, the rats of Shengxian Decoction group were gavaged with an aqueous solution of Shengxian Decoction Chinese medicine granules (0.81 g/kg), the rats of Nintedanib group were gavaged with an aqueous solution of Nintedanib (0.1 g/kg), the rats of Model group and Sham group were gavaged with physiological saline solution (10 mL/kg), once a day for 28 consecutive days. Lung function was detected by awake and unrestrained animal lung function test system; pathomorphologic change in lung tissue was observed by HE and Masson staining; the expressions of α-smooth muscle actin (α-SMA) and Vimentin were detected by Western Blot to assess the degree of lung tissue fibrosis; the contents of Fe2+, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected by chemiluminescence assay, and the expressions of solute carrier family 7 member 11 (SLC7A11) , ferritin heavy chain 1 (FTH1) , glutathione peroxidase 4 (GPX4) were detected by Western Blot, in order to observe the changes in ferroptosis of lung tissues; the expressions of nuclear receptor coactivator 4 (NCOA4), adenylate-activated protein kinase (AMPK), and Beclin1 were detected by Western Blot to observe the changes of iron autophagy in lung tissues. Results: Compared with the Sham group, the lung function indexes of rats in Model group significantly increased respiratory frequency (f) (P<0.01), and peak expiratory flow (PEF) and minute ventilation volume (MV) were significantly decreased (P<0.01); the lung tissue Szapiel score and Ashcroft score were significantly higher (P<0.01); the lung fibrosis indexes of α-SMA and Vimentin were significantly increased (P<0.01); Fe2+, MDA content were significantly increased (P<0.01), SOD, GSH-Px activitve were significantly decreased (P<0.01); the expression of NCOA4, AMPK, Beclin1 protein were significantly increased (P<0.01); the expression of SLC7A11, GPX4, FTH1 protein were significantly decreased (P<0.01). Compared with Model group, the lung function indexes of rats in Shengxian Decoction group, f was significantly decreased (P<0.01), PEF, MV were significantly increased (P<0.01); Szapiel score and Ashcroft score were significantly decreased (P<0.05, P<0.01); α-SMA, Vimentin were significantly decreased (P<0.01); Fe2+, MDA content were significantly decreased (P<0.05, P<0.01), SOD and GSH-Px activive were significantly increased (P<0.01, P<0.05); the expression of NCOA4, AMPK, Beclin1 protein significantly decreased (P<0.05); the expression of SLC7A11, GPX4, FTH1 protein significantly increased (P<0.01, P<0.05). Conclusion: Qi subsidence is an important mechanism of pulmonary dysfunction in IPF, and iron atophagy-ferroptosis pathway is involved in this process; Shengxian Decoction may exert a protective effect on pulmonary function in IPF by regulating the iron atophagy-ferroptosis pathway.