Effect of Atractylenolide Ⅰ on Lung Injury in Rats with Recurrent Respiratory Tract Infection of Lung and Spleen Qi Deficiency by Regulating the PI3K/Akt/mTOR Signaling Pathway / 中药新药与临床药理

ABSTRACT

Objective To investigate the effect of atractylenolideⅠon lung injury in rats with recurrent respiratory tract infection(RRTI)of lung and spleen qi deficiency by regulating phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway.Methods Eighty-four rats were randomly separated into a control group,a model group,a low-dose atractylenolideⅠgroup,a high-dose atractylenolideⅠgroup,a positive drug group,an insulin-like growth factor-1(IGF-1)group,and a high-dose atractylenolide Ⅰ+IGF-1 group,with 12 rats in each group.Except for the control group,the RRTI rat model of lung and spleen qi deficiency was constructed using a combination of fatigue,dietary disorders,and fumigation method with shavings and tobacco among rats in other groups.After the model is successfully copied,the model was administered once a day for 6 weeks.Animal lung function instrument was applied to detect the changes of peak expiratory flow(PEF),forced expiratory volume in first second(FEV1),forced vital capacity(FVC)in rats.The changes of wet/dry mass ratio of lungs in rats were detected.HE staining was applied to detect pathological changes of lung tissue in rats of each group.ELISA was applied to detect the levels of interleukin(IL)-6,tumor necrosis factor-α(TNF-α),malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)in rat lung tissue.Western Blot was applied to determine the protein expressions of p-PI3K,p-Akt,and p-mTOR in rat lung tissue.Results Compared with the control group,rats in the model group showed a decrease in PEF,FEV1 and FVC(P＜0.01)and an increase in the wet/dry mass ratio of lungs(P＜0.01).The alveolar septa in lung tissues had become larger.Pulmonary interstitial edema and a large amount of inflammatory cell infiltration were found.The levels of IL-6,TNF-α and MDA in lung tissue increased(P＜0.01),and the SOD activity decreased(P＜0.01).The protein expressions of p-PI3K,p-Akt,and p-mTOR in lung tissue increased(P＜0.01).Compared with the model group,rats in the low-,high-dose atractylenolideⅠgroups,and positive drug group showed an increase in PEF,FEV1,and FVC,and a decrease in the wet/dry mass ratio of lungs(P＜0.01).Pathologic damage in lung tissue was alleviated.The levels of IL-6,TNF-α,MDA decreased and SOD activity in lung tissue increased(P＜0.01).The protein expressions of p-PI3K,p-Akt,and p-mTOR in lung tissue decreased(P＜0.01),while the corresponding indicators in the IGF-1 group showed opposite trends(P＜0.01).Compared with the high-dose group of atractylenolide I,rats in the high-dose atractylenolide I+IGF-1 group showed a decrease in PEF,FEV1 and FVC,and an increase in the wet/dry mass ratio of lungs(P＜0.01).Pathologic damage in lung tissue was increased.The levels of IL-6,TNF-α,MDA increased and the SOD activity in lung tissue decreased(P＜0.01).The protein expressions of p-PI3K,p-Akt,and p-mTOR in lung tissue increased(P＜0.05,P＜0.01).Conclusion AtractylenolideⅠmay improve lung injury in RRTI rats of lung and spleen qi deficiency by inhibiting the PI3K/Akt/mTOR pathway.