Treatise
WEI Yu, TIAN Xinrong, HE Wenrui, BAI Yunping, ZHAO Hulei, TIAN Yange, LI Jiansheng, ZHAO Peng
China Journal of Traditional Chinese Medicine and Pharmacy.
2024, 39(6):
2872-2878.
Objective: To explore the effect and mechanisms of Baojin Chenfei Formula (BCF) on SiO2-induced silicosis by inhibiting M2 polarization of macrophages via regulating mTORC2-AKT-IRF4 signal. Methods: Thirty-two SPF male SD rats were randomly divided into control group, model group, tetrandrine group (27 mg·kg-1·d-1), and BCF group (9.72 g·kg-1·d-1), 8 in each group. The experimental silicosis model was established by intratracheal injection with SiO2 suspension (50 mg/mL). From the week 7, silicosis rats were treated with tetrandrine or BCF for 2 weeks. The changes of pulmonary function were detected.The pathological changes and collagen deposition of lung tissue were analyzed by HE and Masson staining. The protein levels of COL-Ⅰ, COL-Ⅲ, CD68, CD206 and TGF-β1 expressions were detected by immunohistochemistry. The protein levels of CD206, ARG-1, mTOR, AKT, p-mTORser2481, p-AKTser473 and IRF4 were detected by Western blot. The mRNA levels of CD206 and ARG-1 expressions were detected by Real time PCR. Results: Compared with the normal group, the pulmonary function including VC, TV, Cdyn and Cchord were significantly decreased in the model group (P<0.01); the alveolar structure of model rats was damaged and a large number of inflammatory cells were infiltrated; the protein levels of COL-Ⅰ, COL-Ⅲ, CD68, CD206 and TGF-β1 were significantly increased in the model group (P<0.01). Compared with the model group, the pulmonary function TV, VC, Cchord and Cydn were significantly increased (P<0.05, P<0.01); the pathological changes of the lung tissue were improved; the expressions of COL-Ⅰ,COL-Ⅲ, macrophage markers and fibrosis promoting factor was significantly reduced in BCF-treated rats (P<0.01). In addition, the mRNA and protein of CD206, ARG-1, as well as the protein levels of p-mTORser2481, p-AKTser473, and IRF4, the M2 polarization markers significantly increased in macrophages induced by IL-4 (P<0.05, P<0.01); these changes were significantly inhibited by BCF treatment of high concentration (P<0.05, P<0.01). Conclusion: BCF could improve pulmonary fibrosis in silicosis rat induced by SiO2, and its mechanism may be related to the inhibition of M2 polarization of macrophages via suppressing mTOR signal.