Effect and mechanism of Phillyrin on acute lung injury in septic shock mice

doi:10.13418/j.issn.1001-165x.2024.2.12

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Chinese Journal of Clinical Anatomy ›› 2024, Vol. 42 ›› Issue (2) : 186-190. DOI: 10.13418/j.issn.1001-165x.2024.2.12

Effect and mechanism of Phillyrin on acute lung injury in septic shock mice

Zhang Fan¹, Wei Huanjie¹, Li Long², Ouyang Tao¹, Cai Juan¹, Liang Qiuling¹*, Zeng Yuhui¹

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Abstract

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-1β (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. Beclin1 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.

Key words

Phillyrin / / / AMPK/mTOR/p70S6K signal pathway / / / Autophagy / / / Septic shock / / / Acute lung injury

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Zhang Fan, Wei Huanjie, Li Long, Ouyang Tao, Cai Juan, Liang Qiuling, Zeng Yuhui. Effect and mechanism of Phillyrin on acute lung injury in septic shock mice[J]. Chinese Journal of Clinical Anatomy. 2024, 42(2): 186-190 https://doi.org/10.13418/j.issn.1001-165x.2024.2.12

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