Mechanism of Baojin Chenfei Formula in improving silicosis by suppressing M2 macrophage polarization via the mTORC2-AKT-IRF4 signal pathway
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-β 1 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.
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