Effect of diazoxide with different concentrations on brain tissue in mice model of deep hypothermic low flow

Objective To observe the influence of diazoxide with different concentrations on brain tissue in mice model of deep hypothermic low flow.Methods The C57BL/6 mice (n =240) were randomly and equally divided into 8 groups:sham group,model group,diazoxide (2,5,10 mg/kg) groups and wortmannin + diazoxide (2,5,10 mg/kg) groups.Operation group was subjected to cerebral ischemiareperfusion (I/R):Bilateral common carotid arteries were occluded for 120 min at (18.5 ± 0.5) ℃ and then reperfused and rewarmed afterwards,and the sham operation group experienced the same procedures except occlusion.The protein expression levels of protein kinase B (AKT),p-protein kinase B (p-AKT)and p-glycogen synthase kinase-3β (p-GSK-3β) were detected by using Western blotting at 2,24 and 72 h after I/R,respectively.Five mice taken from each group at 2,24 and 72 h after reperfusion respectively were randomly decapitated and the coronal brain slices were stained with triphenyltetrazolium chloride (TTC) solution.The samples were postfixed and photoed.Results The diazoxide group had the characteristic changes of I/R injury,p-AKT and p-GSK-3β expression levels were higher in diazoxide group than those subgroups and at 24 h after reperfusion (P ＜0.05).The expression of p-AKT and p-GSK-3β was increased at 24 and 72 h after reperfusion in diazoxide (2 ng/kg) group than that in other diazoxide groups (P ＜ 0.05).The diazoxide group had less pathological injury than those groups at 24 h after reperfusion (P ＜0.05).The pathological injury was alleviated at 24 and 72 h after reperfusion in diazoxide (2 mg/kg)group as compared with that in other diazoxide groups (P ＜ 0.05).Conclusion Diazoxide exerts the neuroprotective effects against cerebral I/R injury during deep hypothermia low flow probably by activating the phosphatidylinositol 3 kinase (PI3K)/protein Kinase B (AKT) signal pathway,further up-regulating the expression of p-GSK-3β. Key words: Diazoxide;  Deep hypothermic ;  Cerebral ischemia/reperfusion injury ;  Glycogen synthase kinase-3 ;  Phosphatidylinositol 3 kinase/protein kinase B signaling path way