Study On The Role Of NDRG2 In Reducing Astrocyte Edema Injury Through Regulating AQP4

Objective:To explore the role of Ndrg2 at different time points of cerebral ischemia and edema injury and the role and mechanism of Ndrg2 in astrocyte swelling in the early stage of cerebral ischemia and edema,a mouse model of focal cerebral ischemia and a primary astrocyte oxygen-glucose deprivation cell model were used.Methods:littermate wild-type C57BL/6 mice（WT）were used as controls.The middle cerebral artery occlusion model was constructed by thread occlusion method to simulate transient focal cerebral ischemia-reperfusion injury for 60 min.At different time points of reperfusion:At 3H,6H,12H,24H,48H and 72H,Longa neurological score（8 rats in each group）and brain water content（6 rats in each group）were measured.TTC staining was performed at 24H of reperfusion.To explore the effect of Ndrg2 on reperfusion injury and edema injury at different stages of transient focal cerebral ischemia.Ndrg2-/-and WT primary astrocytes were isolated from Ndrg2^-/-and WT primary astrocytes as controls.An oxygen-glucose deprivation model of primary astrocytes was constructed to simulate ischemia-hypoxia cell injury.Oxygen-glucose deprivation was performed for 120 min,and at different time points of glucose and oxygen restoration:At 1H,4H,8H,12H,24H,and48H,the cell morphology was observed by electron microscopy,the injury of primary astrocytes was analyzed by lactate dehydrogenase leakage test,and the expression and distribution of AQP4 were analyzed by Western blot and cellular immunofluorescence technique.To clarify the role of Ndrg2 in astrocyte edema in the early stage of cerebral ischemic injury.Results:（1）Ndrg2 can reduce the cerebral infarct volume and neurological function score after focal cerebral ischemia-reperfusion injury in mice,and reduce brain edema in the early and late stage of cerebral ischemia.（2）Ndrg2 can alleviate OGD induced primary astrocyte injury and participate in the regulation of primary astrocyte ischemic edema by reducing the expression and redistribution of AQP4 in astrocytes.Conclusion:Ndrg2 can reduce the infarct volume of transient focal cerebral ischemia-reperfusion,reduce the degree of early and late ischemic brain edema,and promote the recovery of neurobehavioral after cerebral ischemia.Ndrg2 has a protective effect on the edema injury of primary astrocytes.At the same time,the loss of Ndrg2 can up-regulate the expression of AQP4 in primary astrocytes and promote the clustering of AQP4 in primary astrocytes.