Effect of berberine on fatty liver ischemia-reperfusion injury in rats: the relationship with endoplasmic reticulum stress in liver tissues

Abstract

Objective To evaluate the effect of berberine on fatty liver ischemia-reperfusion(I/R) injury and the relationship with endoplasmic reticulum stress in liver tissues. Methods Thirty-two male Wistar rats, aged 4 weeks, weighing 100-150 g, were divided into 4 groups(n=8 each) using a random number table method: control group(group C), fatty liver group(group FL), I/R group and berberine group(group BBR ). Rats were fed a normal fat diet for 12 weeks, normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week, and rats only underwent simple laparotomy in group C. Rats were fed a high-fat diet(45% energy originating from fat) for 12 weeks, and the other treatments were similar to those previously described in group C. Rats were fed a high-fat diet(45% energy originating from fat) for 12 weeks, normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week, and then the model of liver I/R injury was established in group I/R. Rats were fed a high-fat diet(45% energy originating from fat) for 12 weeks, berberine solution(300 mg/kg) 3.5 ml was given intragastrically for 4 weeks starting from 9th week, and then the model of liver I/R injury was established in group BBR. Hepatic ischemia was induced by clamping the portal vein, hepatic artery, right gastric vein, and supra- and inferior-hepatic vena cava to perform cold perfusion with 4 ℃ lactated Ringer′s solution lasting for 30 min, followed by reperfusion. The serum triglyceride(TG) concentrations were determined after 4, 8 and 12 weeks of diet. Blood samples were collected at 6 h of reperfusion for measurement of serum aspartate transminase(AST )and alanine transaminase(ALT)concentrations. Livers were removed after blood sampling at 6 h of reperfusion and liver tissues were obtained and stained with oil red O and haematoxylin and eosin for examination of pathological changes and for determination of the expression of Bip, CCAAT/enhancer-binding protein homologous protein(CHOP), protein kinase RNA-like endoplasmic reticulum kinase(PERK) and phosphorylated PERK(p-PERK)(by Western blot). p-PERK/PERK ratio was calculated. Results Compared with group C, the serum TG, ALT and AST concentrations were significantly increased, the expression of Bip and CHOP was up-regulated, p-PERK/PERK ratio was increased(P<0.05), lipid deposition was increased, and liver steatosis was found in group FL. Compared with group FL, the serum AST and ALT concentrations were significantly increased, the expression of Bip and CHOP was up-regulated, p-PERK/PERK ratio was increased(P<0.05), and the pathological changes of liver tissues were accentuated in group I/R. Compared with group I/R, the serum TG, ALT and AST concentrations were significantly decreased, the expression of Bip and CHOP was down-regulated, p-PERK/PERK ratio was decreased(P<0.05), lipid deposition was reduced, and the pathological changes of liver tissues were significantly attenuated in group BBR. Conclusion Berberine can ameliorate fatty liver I/R injury, and the mechanism may be related to inhibiting endoplasmic reticulum stress in liver tissues of rats. Key words: Berberine; Fatty liver; Reperfusion injury; Endoplasmic reticulum; Stress