Protective effect of prostaglandin E1 pretreatment against liver ischemia-reperfusion injury in rats with cholestasis

Objective To investigate the protective mechanism of prostaglandin E1 (PGE1) against liver ischemia-reperfusion injury in rats with cholestasis.Methods A total of 36 male Wistar rats were randomly divided into PGE1 group (PGE group) and normal saline group (NS group) .The rats in the PGE group were treated with continuous pump of PGE1 (0.5 μg/kg/min) from 15 minutes before liver ischemia to 60 minutes of reperfusion, and those in the NS group were given normal saline of the same volume.Common bile duct ligation was performed to establish a rat model of cholestasis.Seven days later, Pringle maneuver was used to perform hepatic inflow occlusion for 15 minutes, and serum levels of enzymes and bilirubin were measured at 1, 6, and 24 hours of reperfusion, as well as the levels of myeloperoxidase (MPO) , tumor necrosis factor α (TNFα) , Bcl-2, Bax, and human heat shock protein 70 (HSP70) and histopathological changes.Results At 1, 6, and 24 hours of reperfusion, there were no significant differences in total bilirubin and direct bilirubin between the two groups (both P>0.05) , and the PGE group had significantly lower levels of alanine aminotransferase, aspartate aminotransferase, MPO, and TNFα than the NS group (all P<0.05) .At 1, 6, and 24 hours of reperfusion, compared with the NS group, the PGE group had a significantly higher level of Bcl-2 and a significantly lower level of Bax (both P<0.05) .At 1 and 6 hours of reperfusion, the PGE group had significantly higher mRNA expression of HSP70 than the NS group (P<0.05) 24="" and="" at="" hours="" of="" there="" was="" no="" significant="" difference="" in="" mrna="" expression="" hsp70="" between="" the="" two="" groups="" p="">0.05) .Compared with the NS group, the PGE group had a lower degree of liver injury, which manifested as reduced hepatocyte swelling and necrosis, clear structures of the hepatic cords and the hepatic sinusoids, regular arrangement of hepatic cords, and widened hepatic sinusoids.Conclusion PGE1 protects the liver with cholestasis against ischemia-reperfusion injury by reducing neutrophil infiltration and Bax expression and upregulating the expression of HSP70 and Bcl-2.