Tacrolimus pretreatment on liver ischemia reperfusion injury in rats / 中华肝胆外科杂志

ABSTRACT

Objective To determine the effects of tacrolimus (FK506) pretreatment on the liver ischemia reperfusion (IR) injury.Methods 32 mature SD rats were randomly assigned into four groups,which were sham-operated group (S),ischemia reperfusion group (IR),low-dose FK506-treated group (L) and high-dose FK506-treated group (H).After the treatment of liver ischemia for 60 minutes and reperfusion for 6 hours,the levels of serum ALT and AST in rats were tested.The TNF-α and IL-1β levels were evaluated by enzyme linked immunosorbent assay.Liver damage was assessed by paraffin sections stained with H&E.The quantitative real-time PCR,the immunohistochemistry and Western blot were used to detect the expression of HMGB1 mRNA and protein with or without FK506 pretreatment.Results The levels of serum ALT [(424.0 ± 137.4)U/L,(291.0 ±42.0)U/L],AST [(554.2 ± 127.7)U/L,(410.2 ±7.0)U/L],TNF-α [(115.1±49.0)ng/L,120.4±28.5) ng/L] and IL-1β [(424.5 ±105.2) ng/L,(612.1 ± 49.6) rig/L] decreased markedly in the group L and group H compared with the group IR (P ＜ 0.05).The liver in the IR group showed hepatic sinusoids congestion,neutrophil infiltration and necrosis.In contrast,tissue damage of the L group and the H group was significantly decreased.The expressions of HMGB1 mRNA and protein reduced significantly when pretreatment with FK506 after reperfusion (P ＜ 0.01).However,there was no significant difference between the group L and group H (P ＞ 0.05).Conclusion FK506 pretreatment can protect the liver by reducing the expression of HMGB1,inhibiting the release of inflammatory cytokines and alleviating cell necrosis after the liver ischemia reperfusion injury in rats.