The Role Of Triggering Receptor Expressed On Myeloid Cell-2(TREM-2)in Renal Ischemia-reperfusion Injury In Mice

Objectives:Open-heart surgery with cardiopulmonary bypass(CPB)is a important way of treatment for congenital heart disease in pediatrics.During the operation,the stop/recovery process of the circulation can cause kidney ischemia-reperfusion injury(ischemic reperfusion injury,IRI).There are up to 30%to 50%of the patients developing varying degrees of kidney damage after CPB surgery,leading to an increased risk of in-hospital death,as well as an increased long-term risk of chronic kidney disease,end-stage kidney disease,and death.At present,the pathogenesis of IRI has not been fully elucidated.In recent years,the mechanism of immune inflammation involved in renal ischemia-reperfusion injury has received more attention.Triggering receptor expressed on myeloid cells 2(TREM-2)are cells that have been found in recent years and belong to the immunoglobulin superfamily.TREM-2 mainly expresses in newly differentiated or activated macrophages,microglia,dendritic cells and osteoclasts.TREM-2 plays an important role in infection and inflammation.It has been showed that TREM-2 reduces inflammation and neuronal apoptosis by regulating the activation of microglia,and then protects against cerebral IRI.In liver IRI,TREM-2 KO mice exhibited enhanced IRI accompanied by augmented liver dendritic cell activation.However,the role of TREM-2 in renal ischemia-reperfusion injury remains unknown.This study will investigate the role and potential mechanisms of TREM-2 in renal ischemia-reperfusion injury in mice.Methods:Male C57BL/6 WT and TREM-2 KO mice were randomly divided into IRI group and control group.The kidney IRI model was established.At 24 h,48 h and 72 h after reperfusion,the mice were sacrificed and samples were collected.The plasma levels of creatinine and urea nitrogen were detected by biochemical method.The renal tissue was prepared for HE staining and the renal tubular injury was semi-quantitatively evaluated.The expression levels of cytokine mRNA were detected using quantitative PCR.Results:1.At 24h,48h and 72h after renal ischemia-reperfusion,the expression levels of TREM-2 in the kidney increased with the reperfusion time,and reached the highest value at 72 h after reperfusion.2.At 48 h after reperfusion,plasma levels of creatinine and urea nitrogen as well as renal injury score in TREM-2 KO mice were significantly reduced compared to those in WT mice.3.At 24 h after reperfusion,the mRNA levels of TNFa,IL-1β,IL-6 and MCP-1 in kidney of TREM-2 KO mice were significantly decreased compared to those in kidney of WT mice.Conclusions:TREM-2 expression levels increased in a time-dependent manner after renal IRI.Deficiency of TREM-2 reduced the plasma levels of creatinine and urea nitrogen,alleviated kidney histologic injury,and decreased expression levels of inflammatory cytokines,thereby improving the prognosis of renal IRI and protecting acute kidney injury.