Objective To investigate the impact of phillyrin on acute lung injury(ALI)in septic shock mice through autophagy mediated by adenosine monophosphate activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)/p70 S6 kinase(p70S6K)signal pathway.Methods Twelve mice were randomly selected as the control group,and the rest of the mice were injected intraperitoneally with 20 mg·kg-1 LPS to construct the model of septic shock,the mice with septic shock were randomly divided into a model group,an Experimental-L,-M,-H group(5 mg·kg-1,10 mg·kg-1,20 mg·kg-1 phillyrin),and an Experimental-H+compound C group(20 mg·kg-1 phillyrin+20 mg·kg-1 AMPK inhibitor compound C),there were 12 mice in each group.The lung dry weight and wet weight were weighed,and the W/D ratio was calculated;the levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-iβ(IL-1β),interleukin-6(IL-6)in BALF,serum endotoxin(ET)and myeloperoxidase(MPO)of lung tissue were detected by ELISA;HE staining was applied to detect pathological changes of lung tissue;Western blot was applied to detect the expression of autophagic proteins microtubule-associated protein-light chain 3(LC3-Ⅱ/Ⅰ),Beclin 1,Ras-associated GTP binding protein 7(Rab7),lysosomal associated membrane protein 2(LAMP2)and AMPK/mTOR/p70S6K signaling pathway proteins.Results In control group,model group,Experimental-L,-M,-H group and Experimental-H+compound C group LC3-Ⅱ/Ⅰ ratios were 1.43±0.14,0.73±0.07,0.81± 0.07,1.12±0.10,1.39±0.13,0.76±0.08,respectively.Beclinl protein levels were 1.05±0.11,0.43±0.05,0.50± 0.05,0.76±0.08,0.98±0.10,0.46±0.05,respectively.Rab7 protein levels were 1.53±0.17,0.67±0.06,0.70± 0.07,1.04±0.10,1.41±0.14,0.69±0.06,respectively.LAMP2 protein levels were 1.47±0.15,0.72±0.07,0.81± 0.08,1.09±0.11,1.35±0.13,0.74±0.07,respectively.p-AMPK/AMPK protein levels were 0.95±0.05,0.33± 0.03,0.39±0.04,0.68±0.07,0.91±0.09,0.36±0.04,respectively.p-mTOR/mTOR protein levels were 0.28± 0.02,0.94±0.06,0.88±0.07,0.57±0.05,0.30±0.03,0.87±0.09,respectively.The protein levels of p70S6K were 0.32±0.07,0.96±0.04,0.90±0.07,0.69±0.06,0.38±0.04,0.92±0.06,respectively.There were statistical differences between the model group and the control group(all P＜0.05).There were statistical differences between Experimental-M,-H group and model group(all P＜0.05).There were significant differences between Experimental-H+compound C group and Experimental-H group(all P＜0.05).Conclusions Phillyrin may improve ALI in septic shock mice by regulating autophagy mediated by AMPK/mTOR/p70S6K signaling pathway.
PhillyrinAMPK/mTOR/p70S6K signal pathwayAutophagySeptic shockAcute lung injury
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