The Effect Of Tacrolimus Pretreatment On Hepatic Ischemia-reperfusion Injury

Objective: The study aimed to investigate the protective role of FK506 pretreatment in hepatic IR injury and the relationships between protective role and HMGB1,HIF-1? and HO-1.Methods: 64 mature SD rats were randomly assigned into two groups with 32 rats per group,which were applied to establish hepatic warm and cold IR models of rats.Each IR model was divided into four groups,namely sham-operated group,ischemia-reperfusion group(Control group),low-dose FK506-treated group and high-dose FK506-treated group.After the reperfusion for 6 h,the levels of serum ALT and AST were tested.The TNF-?,IL-6 and IL-1? levels were evaluated by enzyme linked immunosorbent assay(ELISA).Liver damage was assessed by paraffin sections stained with H&E.The quantitative real-time PCR(RT-q PCR)was used to test HMGB1 and HO-1 m RNA;the immunohistochemistry were used to detect the distribution of HMGB1;and the expressions of HMGB1,HIF-1? and HO-1 protein were measured by Western blot.Results: The levels of serum ALT,AST,TNF-?,IL-6 and IL-1? decreased markedly in the treated groups compared with the untreated group in warm and cold IR models.The liver in the ischemia-reperfusion group of warm and cold IR models all showed hepatic sinusoids congestion,neutrophil infiltration and necrosis.In contrast,tissue damage of the different-doses FK506-treated groups was significantly decreased.Compared with the sham-operated group,the expression of HMGB1 m RN A and protein demonstrated a marked increase in the ischemia-reperfusion group,but decreased in the FK506-treated groups.The expressions of HIF-1? and HO-1 insreased markedly in low-dose FK506-treated rats of warm and cold IR models.Conclusion: FK506 pretreatment can alleviate hepatic ischemia-reperfusion injury in rats by reducing the expression of HMGB1,inhibiting the release of inflammatory cytokines and upregulating the expressions of HIF-1? and HO-1.