Research of the effective mechanism of rosiglitazone to biliary ischemia-reperfusion injury in autologous liver transplantation / 中华急诊医学杂志

ABSTRACT

Objective To explore the effective molecular mechanism of PPAR-γligands rosiglitazone to biliary ischemia-reperfusion injury in autologous liver transplantation. Method A total of 40 SD rats were randomly (random number) divided into sham operation group (SO), ischemia - reperfusion group (Ⅰ/R), rosiglitazone (ROS) and GW9662 group, with 10 ones in each. The models, rat biliary ischemiareperfusion injury of autologous liver transplantation, were made by modified two-cuff technique. Tissues of the liver and bile ducts and blood of those models were evaluated by pathological and biochemical methods to make sure the models were made successfully or not. SO group suffered autologous orthotopic liver transplantation, and L/R group suffered both that and ischemia-reperfusion. ROS group were injected rosiglitazone (0.3mg/kg) via portal vein after having been done all as I/R. GW9662 group suffered all as ROS, and 10min later ,they were injected GW9662(0.3mg/kg) via portal vein. 4h after the experiment, tissues of livers and bilary ducts were taken to be tested by immunohistochemistry method, and the blood punctured from the right ventricular were taken to be determined by ELISA. ANOVA was used for statistical analysis.Results IL-1β, TNF-α and IL-6 were mainly expressed in the cytoplasm of hepatocytes and bile duct cells,while NF-κB was expressed both in the cytoplasm and nuclei. Expression of those proteins in L/R and GW9662 group was increased, significantly higher when compared to the SO and ROS (P ＜ 0.05). IL-1β,TNF-α and IL-6 in rat serum were simultaneously increased, and significantly higher than SO(P ＜0.05).Compared with the SO, expressions of the IL-1 β,TNF-α and IL-6 were not significantly changed in ROS (P＞ 0.05 )but significantly increased in GW9662. Conclusions PPAR-γ ligand rosiglitazone took protective role in biliary ischemia-reperfusion injury in autologous liver transplantation. The mechanism correlates with the release of the IL-lα, IL-1β and TNF-α and other inflammatory mediators, which decreased as the expression of NF-κB inhibited by its antagonist.