Study on Therapeutic Effect and Mecha-nism of Buyang Huanwu Decoction(补阳还五汤)in Treatment of Model Mice with Radiation Pneumonitis
Objective:To explore the effect of Buyang Huanwu Decoction(补阳还五汤)on model mice with radiation pneumonitis(RP),and to evaluate its efficacy and potential mechanism from phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway.Methods:A total of sixty C57BL/6J female mice were randomly divided into blank group,model group,prednisone group,low-dose,medium-dose and high-dose groups of Buyang Huanwu Decoction,with 10 mice in each group.The blank group was not irradiated,while the remaining 5 groups of mice were induced to establish the RP models using an X-ray biological radiation irradiator at a dose of 15 Gy.After modeling,the prednisone group(0.325 g·kg-1·d-1)and the low-dose,medium-dose and high-dose groups of Buyang Huanwu Decoction(18.6 g·kg-1·d-1,37.2 g·kg-1·d-1,74.4 g·kg-1·d-1)were given corresponding drugs by gavage according to body weight.The blank group and model group were given normal saline(20 mL·kg-1·d-1)by gavage once a day for 28 consecutive days.The body weight and wet weigh index of lung of each group were observed.Hematoxylin-eosin(HE)staining was used to observe the pathomorphological changes of lung tissue.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of interleukin-17(IL-17),hydroxyproline(HYP),type Ⅰ collagen(ColI)and transforming growth factor-β1(TGF-β1)in lung tissue.The protein expression differences of PI3K,phosphorylated(p)-PI3K,Akt,p-Akt,mTOR and p-mTOR in lung tissue were detected by Western blot.Results:Compared with the blank group,the body weight of the mice in the model group was significantly decreased,and the wet weigh index of lung was significantly increased(P<0.01).Compared with the model group,the body weight of the mice in each drug group was increased and the wet weigh index of lung was decreased(P<0.01).The lung tissue structure of the model group was severely damaged,with a large amount of inflammatory exudation in the lumen,widening of the alveolar septum,and congestion,the alveolar structure was incomplete,the alveoli collapsed,and the alveoli were severely destroyed.The lung tissue structure of each dose group of Buyang Huanwu Decoction was relatively complete,and the degree of inflammatory cell infiltration was lower,and the degree of inflammation was improved compared with the model group.Compared with the blank group,the levels of IL-17,HYP,ColI in lung tissue and TGF-β1 in serum of the model group were significantly increased(P<0.01).Compared with the model group,the levels of IL-17,HYP,ColI in lung tissue and TGF-β1 in serum of mice in the high-dose and medium-dose groups of Buyang Huanwu Decoction were significantly decreased(P<0.05 or P<0.01).Compared with the blank group,the expression levels of p-Akt/Akt,p-PI3K/PI3K and p-mTOR/mTOR in lung tissue of the model group were significantly increased(P<0.05 or P<0.01).Compared with the model group,the expression levels of p-Akt/Akt,p-PI3K/PI3K and p-mTOR/mTOR in lung tissue of the high-dose and medium-dose groups of Buyang Huanwu Decoction were significantly decreased(P<0.05 or P<0.01).Conclusions:Buyang Huanwu Decoction had a good therapeutic effect on RP in model mice,which can improve lung tissue structure and reduce inflammation degree,and its mechanism may be related to the inhibition of PI3K/Akt/mTOR pathway.