Tacrolimus pretreatment on liver ischemia reperfusion injury in rats

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) ng/L] decreased markedly in the group L and group H compared with the group IR (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. Key words: Tacrolimus; Liver; Ischemia reperfusion; High mobility group box 1 protein, HMGB1; Liver protection