SIRT5 alleviates hepatic ischemia and reperfusion injury by diminishing oxidative stress and inflammation via elevating SOD1 and IDH2 expression.

Hepatic ischemia/reperfusion (I/R) injury, a common and unavoidable pathophysiological process during liver transplantation or resection operation, may impede postoperative liver function recovery, and its mechanism and targeted therapy remain largely unknown. SIRT5 is a well-known deacetylase and participates in the regulation of many physiological and pathological processes, including I/R. The role of SIRT5 in I/R is controversial or tissue-specific, restricting I/R progression in the heart while deteriorating injury in the kidney and brain, while its effect on hepatic I/R remains unclear. In this study, we investigated the function of SIRT5 in hepatic I/R using AAV8 and lentivirus to overexpress SIRT5 in vivo and in vitro. The data showed that SIRT5 overexpression alleviated liver I/R injury in mice and hypoxia/reoxygenation treated AML-12 cells. Moreover, gain- and loss-of-function of SIRT5, SOD1 and IDH2 experiments in AML-12 were performed. Our results demonstrated that SOD1 and IDH2 knockdown abolished the effect of SIRT5 on restraining oxidative stress and inflammation. Therefore, our work revealed that SIRT5 may alleviates hepatic I/R injury by diminishing oxidative stress and inflammation via up-regulating the SOD1 and IDH2 expression, which enriches the theory and therapeutic strategies of hepatic I/R injury.