通腑理肺汤调节PI3K/AKT/mTOR信号通路介导自噬对脓毒症急性肺损伤的影响OA

Objective To investigate the effects of Tongfu Lifei Decoction(通腑理肺汤,TFLFD)on sepsis-associated acute lung injury(SA-ALI)in rats by regulating autophagy through the PI3K/AKT/mTOR signaling pathway,and to explore the underlying mecha-nism by which TFLFD alleviates lung injury.Methods Thirty SPF rats were randomly divided into five groups(n=6):a blank control group,a model group(LPS,5 mg·kg⁻¹),a low-dose TFLFD group(7.18 g·kg⁻¹),a high-dose TFLFD group(14.26 g·kg⁻¹),and a clarithromycin group(45 mg·kg⁻¹).Pulmonary edema was evaluated by lung index and wet-to-dry weight ratio(W/D),and lung injury was assessed by hematoxylin-eosin(HE)staining.The expression of vascular cell adhesion molecule-1(VCAM-1)in lung tissue was observed by immunohistochemistry(IHC).The levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA expression levels of PI3K and AKT were mea-sured by real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR).The protein expression levels of AKT,p-AKT,PI3K,p-PI3K,mTOR and p-mTOR in rat lung tissue were determined by Western blot(WB).The expression levels of Beclin 1,LC3 and p62 in lung tissue were detected by immunofluorescence(IF).Results Compared with the model group,both low/high-dose TFLFD groups and clarithromycin group showed significantly decreased lung index and W/D ratio,alleviated alveolar structure damage and reduced inflammatory cell infiltration in lung tissue.Compared with the model group,the high-dose TFLFD group and clarithromy-cin group exhibited decreased lung injury scores.The expression levels of VCAM-1,IL-6,TNF-α and IL-1β in lung tissue were signifi-cantly decreased.The mRNA expression levels of PI3K and AKT,as well as the phosphorylation levels of p-PI3K,p-AKT and p-mTOR protein,were significantly increased.The expression levels of Beclin 1 and LC3 were increased,while the expression level of p62 was decreased.Conclusion TFLFD exerts a protective effect against the progression of SA-ALI.Its mechanism may be related to activating the PI3K/AKT/mTOR signaling pathway,further promoting autophagy activation,reducing the production of pro-inflammatory cyto-kines,promoting vascular endothelial repair,alleviating pulmonary edema,thereby relieving lung injury and treating SA-ALI.