TIM-1 attenuates the protection of ischemic preconditioning for ischemia reperfusion injury in liver transplantation

摘要

Ischemic preconditioning (IPC) has been introduced to protect grafts against ischemic reperfusion injury (IRI) during liver transplantation (LT) in recent years. However, the underlying molecular mechanisms of IPC are not fully understood. We aimed to confirm whether the efficacy of IPC is dependent on T cell Immunoglobulin and Mucin domain-containing molecules-1 (TIM-1). Quantitative real-time reverse transcription PCR and western blotting were used to detect the expression of genes of interest. Graft function was assessed using the levels of alanine transaminase (ALT) and aspartate transaminase (AST), percentage of apoptosis cells and pathological examination. IPC treatment alleviated graft function after ischemic reperfusion. AST, ALT, CD68, CD3 positive cells and tissue myeloperoxidase activity were decreased significantly by IPC. IPC decreased the expressions of the cytokines and chemokines. Compared with the IRI group, TIM-1 expression and TIM-1 positive cells were inhibited significantly in the IPC group. TIM-1 blockage abolished the protective effect of IPC on IRI damage. IPC could not further improve graft function and decrease the sequestration of immune cells after blocking TIM-1 signaling. IPC is a convenient therapeutic strategy against IRI during LT. The benefit of IPC depends on TIM-1 signaling.