Methylprednisolone alleviates lipopolysaccharide-induced liver injury via activating autophagy / 中华急诊医学杂志

ABSTRACT

Objective To investigate the effects and underlying mechanisms of methylprednisolone (MP) on liver injury induced by lipopolysaccharide (LPS).Methods Total of 48 C57BL/6 mice (8-week old) were randomly divided into the control group,LPS-induced endotoxemia model (1 h,2 h,4 h,8 h,24 h,48 h) and intervention group with MP therapy (n =6).Mice were intraperitoneally injected withLPS (20 mg/kg) for indicated time (1 h,2 h,4 h,8 h,24 h,48 h),and MP (20mg/kg) was intraperitonealinjected into micetointervene LPS-induced liver injury.Saline was used as control.Pathological changes of liver tissues were analyzed by hematoxylin & eosin (HE) staining.The serum levels of ALT,TBIL and TBA were determined,and the mRNA levels of TNF-α,IL-6,IL-1β and the protein levels of P62,LC3 Ⅱ/Ⅰ in livers were detected by real time-PCR and Western-blot.Results (1) MP therapy protects mice against LPS-induced liver injury at the dose of 20 mg (kg · d).The pathological sections showed that the structure of hepatic lobule,the hepatocyte vacuolar degeneration,eosinophilic degeneration were improved in LPS + MP/group compared with LPS group;(2) The serum levels of ALT,TBIL,TBA in LPS + MP group was significantly decreased compared with LPS 48 h group [(63.40 ±11.55) vs.(104.50±29.34) U/L,(0.37 ±0.08) vs.(0.52 ±0.12) μmol/L,(4.67 ±2.58) vs.(10.33 ± 2.34) μmol/L,P =0.009,P =0.032,P ＜ 0.01];(3) The mRNA levels of TNF-α,IL-6,IL-1β in LPS + MP group was significantly lower than that of LPS 48 h group [(4.18 ±0.81) vs.(10.09 ±4.73),(0.31 ±0.14) vs.(1.06 ±0.68),(0.17 ±0.05) vs.(1.22 ±0.50),respectively,all P ＜0.05];(4) LPS activated autophagy within 2h after LPS treatment.Then,autophagy was suppressed from 2h to 24h after LPS treatment indicated as the decreased expression of LC3 Ⅱ/Ⅰ.Interestingly,MP treatment significantly reversed LPS-suppressed autophagy showing that the protein level of LC3 Ⅱ/Ⅰ was significantly increased in LPS + MP group compared with LPS 48 h group.Conclusions MP therapy protects mice against LPS-induced liver injury and inflammation,partially due to activation of autophagy in livers.