Berberine prevents steatotic liver ischemia reperfusion injury by inhibiting endoplasmic reticulum stress and autophagy

Abstract

Objective To explore the effect of berberine (BBR) on steatotic liver ischemia reperfusion injury and analyze the role of endoplasmic reticulum stress and autophagy. Methods Thirty-four Wistar rats were fed with a high-fat diet for 12 weeks and 2 rats were randomly selected after 8 weeks to observe pathological changes and confirm the model of steatotic liver successfully. Then before opening and closing abdominal cavity, 32 rats were divided into I/R group (normal saline was intragastrically 4 weeks before performing cold I/R treatment), BBR group (normal saline was replaced by BBR, BBR was intragastrically at a dose of 300 mg·kg-1·d-1 weeks and others were the same as I/R group) and TG group (TG was intraperitoneally at a dose of 0.2 mg·kg-1 24h pre-operation and others were the same as BBR group ). Then the rats were sacrificed at 6h post-reperfusion. Blood samples were collected from inferior vena cava and hepatic tissues harvested. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected, histopathologic changes observed by Hematoxylin & Eosin (HE) staining, oxidative stress and inflammation determined by ELISA kit and the expressions of p-PERK, CHOP, Bip, LC3, Beclin-1 and p62 detected by Western blot. Results As compared with Sham group, the serum levels of ALT and AST were significantly higher in I/R, BBR and TG groups (P<0.05). And hepatic histological changes were severe and oxidative stress increased in parallel with the enhancement of pro-inflammation (P<0.05). In BBR group, the level of hepatic enzymes declined, liver injury was milder, oxidative stress decreased and pro-inflammation was lesser compared with I/R and TG groups (P<0.05). Additionally, as compared with sham group, the expressions of p-PERK, CHOP, Bip, LC3, Beclin-1 and p62 were up-regulated in I/R and BBR groups (P<0.05). TG group increased the levels of LC3, Beclin-1 and p62 (P<0.05). Interestingly, compared with I/R group, BBR pretreatment down-regulated the expressions of p-PERK, CHOP, Bip, LC3, Beclin-1 and p62 (P<0.05). TG group had the higher expressions of LC3, Beclin-1 and p62 than those of BBR group (P<0.05). Conclusions BBR pretreatment can protect steatotic liver ischemia reperfusion injury. And the mechanisms may be attributed to the inhibitions of endoplasmic reticulum stress and autophagy. Key words: Rat; Steatotic liver; Berberine; Ischemia reperfusion injury; Endoplasmic reticulum stress; Autophagy