ABSTRACT
Objective To study the protective effect of minocycline against ischemia-reperfusion injury after liver transplantation and its molecular mechanism after circulatory death in rats.Methods The rat donation after circulatory death (DCD) liver transplantation model was established by using magnetic-ring method.The donor and recipient were male SD rats.The rats were divided into sham operation group (SHAM group),liver transplantation group,minocycline group (MIN group),atractyloside + minocycline group (ATR + MIN group),24 rats in each group.In the MIN group,10 mg/kg minocycline was injected through the dorsum vein of the penis after reperfusion.The ATR + MIN group was injected with 2 mg/kg atractyloside.The open status of mitochondrial permeability transition pore (mPTP) was detected at 2,6,and 24 h after operation.Western blotting and immunohistochemistry were used to detect the expression of caspase3 and cyt c.Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined.Liver tissues were stained with hematoxylin-eosin (HE) and pathological changes were evaluated by Suzuki's standard.The survival of each group was calculated.Results As compared with liver transplantation group and ATR+ MIN group,the mPTP opening of MIN group decreased (P＜0.05),the expression of caspase3 and cyt c and the serum ALT and AST levels decreased significantly (P＜0.05),liver tissues injury was alleviated (P＜0.05),and the survival rate increased significantly after 30 days (P ＜0.05).There was no significant difference between liver transplantation group and ATR + MIN group (P ＞ 0.05).Conclusion Minocycline reduces ischemia-reperfusion injury in DCD liver transplantation in rats probably by inhibiting the mPTP opening,and preventing cyt c release and caspase3 activation to reduce hepatocyte apoptosis.This effect can be blocked by mPTP opener.