Title: Methylprednisolone alleviates lipopolysaccharide-induced liver injury via activating autophagy
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...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 LC3Ⅱ/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.
Key words:
Methylprednisolone; Autophagy; Endotoxemia; Liver injury; MiceRead More
Publication Year: 2017
Publication Date: 2017-12-10
Language: en
Type: article
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