腺苷A_(2A)受体在慢性间歇低氧小鼠空间记忆损害中的作用  

Effect of Adenosine A_(2A) Receptor on Memory Impairment in Mice Following Chronic Intermittent Hypoxia

作　　者：李秀翠[1] 张子龙 李轩 马伊璇 李慧敏 薛铭杰 洪静怡 蔡晓红[2] LI Xiucui;ZHANG Zilong;LI Xuan(Department of Pediatric Neurology,The Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical Uni-versity,Zhejiang 325027,China)

机构地区：[1]温州医科大学附属第二医院育英儿童医院儿童神经科,325027 [2]温州医科大学附属第二医院育英儿童医院儿童呼吸科,325027 [3]温州医科大学第二临床医学院,325000 [4]温州医科大学精神医学院,325000 [5]温州医科大学口腔医学院,325000 [6]台州市妇女儿童医院儿科,318000

出　　处：《医学研究杂志》2023年第5期28-33,共6页Journal of Medical Research

基　　金：国家自然科学基金资助项目(面上项目)(81870073);浙江省温州市基础性科研项目(Y20210009);浙江省基础公益研究计划项目(LQ23H010002)。

摘　　要：目的探讨腺苷A_(2A)受体(A_(2A)receptor,A_(2A)R)在慢性间歇低氧所致小鼠记忆损害中的作用及机制。方法取42只清洁级健康雄性C57BL/6小鼠,随机分为空白对照组、空气模拟对照组、慢性间歇低氧模型组(模型组)、模型组+A_(2A)R激动剂CGS21680组(A_(2A)R激动剂组)、模型组+A_(2A)R抑制剂SCH58261组(A_(2A)R抑制剂组)、模型组+A_(2A)R基因敲除组(A_(2A)R敲除组)及模型组+DMSO溶剂对照组(溶剂对照组),每组6只。采用八臂迷宫测试各组幼鼠参考记忆错误、工作记忆错误及总错误数,尼氏染色法观察并计算海马CA1区神经元数量,膜片钳技术进行海马CA3-CA1区神经元长时程增强重要参数场兴奋性突触后电位(field excitatory postsynaptic potential,fEPSP)的测定,蛋白免疫印迹法检测海马突触融合蛋白syntaxin表达水平。结果与对照组比较,模型组参考记忆错误、工作记忆错误及总错误次数均升高(P<0.01),fEPSP斜率及syntaxin蛋白水平下降(P均<0.01);与模型组比较,A_(2A)R抑制剂组、A_(2A)R基因敲除组参考记忆错误、工作记忆错误及总错误次数减少(P<0.05),fEPSP斜率及syntaxin蛋白水平升高(P均<0.05),A_(2A)R激动剂组参考记忆错误、工作记忆错误及总错误次数增多(P<0.01),fEPSP斜率及syntaxin蛋白水平下降(P均<0.05)。结论慢性间歇低氧可通过激活腺苷A_(2A)R,导致海马CA3-CA1区神经元突触可塑性降低,造成小鼠空间记忆损害;敲除或抑制腺苷A_(2A)R可改善海马神经元突触可塑性,减轻小鼠记忆损害。Objective Our study is aimed to investigate the effect and mechanism of A_(2A)R on learning and memory impairment induced by chronic intermittent hypoxia(CIH)in mice.Methods Forty-two healthy and male C57BL/6mice were randomly divided into 7groups:control group,air simulation control group,CIH model group(model group),A_(2A)R agonist CGS21680group exposed with CIH(A_(2A)R agonist group),A_(2A)R antagonist SCH58261group exposed with CIH(A_(2A)R antagonist group),A_(2A)R gene knockout mouse group exposed with CIH(A_(2A)R-/-group)and DMSO solvent control group(solvent control group),with 6mice in each group.The number of reference memory errors(RME),working memory errors(WME),and total errors(TE)were measured by the eight-arm maze test.Nissl staining was analyzed to assess neuronal viability in the hippocampus.Field excitatory postsynaptic potential(fEPSP)of neurons,an important parameter of the long-term potentiation(LTP)was determined in hippocampal CA3-CA1 region via the patch clamp tech-nique.The expression level of synaptic fusion protein(syntaxin)in the hippocampus was detected by western blot.Results Compared with the control group,the WME,RME and TE in CIH model group were increased(P<0.01),followed a decreasing neuronal viability was showed in the hippocampal CA1 region(P<0.01),while the slope of fEPSP and the protein level of syntaxin in CIH model group were significantly decreased(P<0.01).Compared with the model group,the WME,RME and TE in A_(2A)R antagonist group and A_(2A)R(-/-)group were significantly decreased(all P<0.05),followed an increasing neuronal viability(all P<0.01),and the slope of fEPSP and the level of syntaxin were significantly increased(all P<0.05),while the WME,RME and TE in A_(2A)R agonist group were increased(all P<0.01).The slope of fEPSP and the level of syntaxin decreased significantly(both P<0.05).Conclusion Chronic intermittent hypoxia can reduce the synaptic plasticity in hippocampal CA3-CA1 region by activating the adenosine A_(2A)receptor,resulting in impaired learning and me

关 键 词：慢性间歇低氧 记忆损害 腺苷A_(2A)受体 突触可塑性 

分 类 号：R72[医药卫生—儿科]