腺苷激酶活化在幼鼠癫痫形成中的作用

Role of adenosine kinase activation in epileptogenesis in immature rats

目的:探讨腺苷激酶(ADK)在幼鼠癫痫形成中的作用和相关机制。方法:海人藻酸(KA)诱导幼鼠痫性发作(SE),检测静止期(SE后14 d)和慢性自发性癫痫(SRS)形成期(SE后42 d)ADK的表达;部分幼鼠腹腔注射腺苷受体拮抗剂ABT⁃702,分为对照组(NC)、致痫组(SE)和SE后ABT⁃702干预组(SE+ABT⁃702)。观察SRS在各组的差异,检测SRS形成期各组ADK,腺苷A1受体(A1R)和A2αR蛋白表达差异;尼氏染色观察海马神经元丢失和促炎性因子IL⁃18和IL⁃1β的表达在各组的差异。结果:KA诱导SE发作后,静止期及SRS形成期海马区ADK表达均增加;ABT⁃702抑制SRS慢性期ADK的活化,降低SRS发生率,抑制抑制海马神经元丢失;SE组ADK活化激活A2αR,诱导促炎性因子IL⁃18和IL⁃1β,ABT⁃702抑制A2αR及促炎性因子IL⁃18和IL⁃1β的活化。结论:SE诱导ADK持续活化,癫痫形成期腺苷A2α受体被激活,诱导海马神经元丢失和促炎性因子IL⁃18和IL⁃1β释放,在幼鼠慢性癫痫形成发挥重要作用。

Objective:To investigate the role and mechanism of adenosine kinase(ADK)in epileptogenesis in immature rats.Methods:Kainic acid(KA)induced epileptic seizures(SE)in immature rats.After SE onset,the immature rats were injected intraperitoneally with ABT⁃702,the adenosine receptor an⁃tagonist.They were divided into control group(NC),epileptogenic group(SE)and ABT⁃702 inter⁃vention group(SE+ABT⁃702).The morbidity of spontaneous recurrent seizures(SRS)in chronic phase was observed,and the expression of ADK in quiescent phase(14 d after SE attack)and SRS for⁃mation phase(42 d after SE)were detected;adenosine receptors A1R and A2αR were also detected in the three groups during SRS formation.Hippocampal neuron loss by Nissl staining and the expression of proinflammatory factors IL⁃18 and IL⁃1βwere observed in each group.Results:After SE attack in⁃duced by KA,the expression of ADK in hippocampus increased during stages of quiescence and SRS;Inhibition of ADK activation after SE can reduce SRS rate and hippocampal neuron loss;ADK inhibi⁃tor ABT⁃702 can reverse the activation of A2αR and alleviate proinflammatory factors IL⁃18 and IL⁃1βrelease in epileptogenesis.Conclusion:Epileptic seizures induce continuous activation of ADK,which plays an important role in the formation of chronic epilepsy by activating A2αR,increasing pro⁃inflammatory factors IL⁃18 and IL⁃1β,and inducing hippocampal neuronal loss in immature mice.