Study on the Role of Adenylate Kinase 4 in Nerve Injury in the Early Stage of Cerebral Ischemia
Objective Neuronal damage caused by insufficient cerebral blood supply is the direct cause of neurological dysfunction in ischemic stroke.Mitochondrial dysfunction is closely related to neuronal damage.Adenylate kinase 4(AK4)is a key factor in energy metabolism.The purpose of this study is to explore the role of AK4 in early nerve injury after cerebral ischemia.Methods The study sample consisted of 60 male C57BL/6J mice,3 to 4 weeks of age and 18 to 20 g body mass,constructed neuron-specific overexpressing AK4 adeno-associated virus(AAV)-unloaded(AAV-Ctrl group)and AAV-AK4 overexpressing mice(AAV-AK4 group).A mouse middle cerebral artery occlusion(MCAO)model was established to simulate cerebral ischemia in vivo,and the protein expression level of AK4 was determined by western blot after 1 h,2 h and 3 h of ischemia,respectively.After 3 h of pure ischemia,2,3,5-triphenyltetrazolium chloride(TTC)staining was used to detect the degree of ischemic brain tissue injury,and TUNEL method was used to detect neuronal apoptosis.Results The experimental results showed that AK4 protein expression on infarct side(Ⅰ)began to be down-regulated compared with non-infarct side(NI)at MCAO 2 h and MCAO 3 h,and MCAO 3 h was the most significant,with statistical significance(P＜0.05).Compared with AAV-Ctrl group,after 3 h of MCAO,the volume of cerebral infarction in AAV-AK4 group was significantly reduced,and the number of neuronal apoptosis in AAV-AK4 group was significantly reduced compared with AAV-Ctrl group,with statistical significances(P＜0.05).Conclusion Overexpression of AK4 in neurons in the early stage of cerebral ischemia can significantly reduce the volume of cerebral infarction,inhibit neuronal apoptosis and play a neuroprotective effect.AK4 may be a new target for intervention of neuronal injury in the early stage of cerebral ischemia.
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