The effect and mechanism of tacrolimus pretreatment on cold ischemia reperfusion injury of transplanted liver in rats / 中华肝胆外科杂志

ABSTRACT

Objective:To investigate the roles of tacrolimus pretreatment on hepatic ischemia reperfusion injury (IRI) and its possible mechanism in a rat autologous orthotopic liver transplantation (AOLT) model.Methods:For 24 specific pathogen free 8-10 week male Sprague Dawley rats (220-250g) were randomly and equally divided into three groups. The abdomen of sham-operated group was only opened and closed; the treatment with tacrolimus was administered via dorsal penile vein before the experiment in tacrolimus-pretreated group; the AOLT group and tacrolimus-pretreated group were set to construct the AOLT IRI rat models. The levels of ALT, AST, tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β) in serum were tested after the reperfusion. The change of liver structure was evaluated by H&E staining. The quantitative real-time PCR (RT-qPCR) and Western blot assay were used to test the mRNA and protein level of hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 (HO-1).Results:The levels of serum ALT (1 332.0±52.8) U/L and AST (2 472.0±257.8) U/L in the AOLT group were higher than the levels in the sham-operated group (65.0±17.4)U/L, (222.3±45.2) U/L and tacrolimus-pretreated group (789.9±54.0) U/L, (533.4±31.6) U/L. The differences were significant ( P<0.05). And in the tacrolimus-pretreated group there were less lesions in the liver than in the AOLT group. The serum level of TNF-α and IL-1β of the AOLT group were increased than the sham-operated group and tacrolimus-pretreated group, and the differences were significant ( P<0.05). Compared with the AOLT group, the expressions of HIF-1α and HO-1 were increased significantly after the tacrolimus pretreatment ( P<0.05). Conclusion:Tacrolimus pretreatment could reduce rats hepatic cold IRI by inducing the expressions of HIF-1α and HO-1, and inhibiting the production of inflammatory cytokines.