Effects Of Adenosine Kinase Inhibitor On Oxidative Stress And Neuronal Apoptosis In The Early Stage Of Focal Ischemia-Reperfusion Injury

BackgroundAdenosine is an acute endogenous neuroprotective agent in the presence of cerebral ischemic injury.Adenosine kinase(ADK)is a key enzyme for regulating adenosine levels.ADK,is also endogenously regulated after stroke,and its expression is decreased following onset of injury thus potentiating the adenosine surge.Thus,expression levels of ADK might have a crucial role in determining the brain’s susceptibility to stroke-induced injury.Adenosine kinase inhibitor(ABT-702)is an effective,adenosine competitive reversible adenosine kinase inhibitor,The inhibition of ADK expression at the pharmacological level will be the focus of this study.We established rat focal ischemia-reperfusion model,ABT-702 was given early in the treatment window to observe the effect of ABT-702 on oxidative stress and neuronal apoptosis in early stage of ischemia-reperfusion injury.ObjectiveTo observe the effects of adenosine kinase inhibitor(ABT-702)on oxidative stress and neuronal apoptosis in the early stage of focal cerebral ischemia-reperfusion injury in rats.Method1.Sixty healthy Sprague-Dawley(SD)male rats(250~300g)were randomly divided into 3 groups: Sham-operated group,ischemia-reperfusion group,ABT-702 intervention group.The IR group and the ABT-702 intervention group were divided into two subgroups according to the time point of reperfusion,namely IR 2h group,IR 6h group,ABT-702 2h group and ABT-702 6h group.There are twelve mice in each group.2.The activity of superoxide dismutase(SOD),The content of malondialdehyde(MDA)in the lipid peroxidation product and the activity of apoptosis factor Caspase 3 in the ischemic penumbra were detected by enzyme-linked immunosorbent assay(ELISA).3.Data((x|-)±s)expressed in the form and the data were analyzed by SPSS 22.0 statistical software for one-way ANOVA.The LSD-t test was used to compare the two groups,the test level α = 0.05 was statistically significant,the changes of SOD activity,MDA content and activity of Caspase 3 in each group were compared.Result1.Compared with Sham group,the activity of SOD increased gradually and the activity of Caspase 3 gradually increased with the time of reperfusion;2.The ABT-702 had significant difference compared with IR group at 2h and 6h(P< 0.05);3.The activity of Caspase 3 in ABT-702 and IR groups was insignificant at 2h(P> 0.05),however,the activity of Caspase 3 decreased significantly at 6h in ABT-702 group compared with IR group(P< 0.05).Conclusion1.With the prolongation of ischemia-reperfusion time,the more severe oxidative damage and the more neuronal cell apoptosis in rat brain tissue;2.Adenosine kinase inhibitor plays an antioxidant role in the early stage of focal ischemia-reperfusion injury in rat brain by inhibiting the production of free radicals;3.Adenosine kinase inhibitor can reduce the apoptosis of neuronal cells in ischemic penumbra,and protect the early stage of cerebral ischemia-reperfusion injury.