腺苷A_(2A)受体在小鼠大脑中动脉局灶缺血损伤中的作用及机制  

Role of adenosine A_(2A) receptor in ischemic brain injury induced by transient middle cerebral artery occlusion in mice

作　　者：田洪[1] 段炜[1] 桂莉[1] 郑健[1] 

机构地区：[1]第三军医大学新桥医院神经内科,重庆400037

出　　处：《第三军医大学学报》2009年第10期910-913,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金青年基金(30800354)~~

摘　　要：目的探讨阻断腺苷A2A受体对神经元缺血性损伤的影响及其可能机制。方法将腺苷A2A受体基因敲除(A2ARKO)小鼠24只及同窝野生型(A2ARWT)小鼠24只分为A2ARKO组和A2ARWT组,每组下设脑缺血2h(各6只)、脑缺血后再灌注22h(各6只)和脑缺血后再灌注46h(各12只)3个时相点,另外9只A2ARWT小鼠设为假手术组。线栓法制作大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)模型,脑组织切片甲酚紫染色结合图象分析技术测定脑梗死体积,干湿质量法测定脑组织含水量,免疫组化染色检测钙结合蛋白(Calbindin D-28k,CB)和水通道蛋白4(aquaporin,AQP4)。结果在脑缺血2h、脑缺血后再灌注22h和脑缺血后再灌注46h,测定A2ARKO组的脑梗死体积均小于A2ARWT组的梗死体积;与A2ARWT组比较,A2ARKO组脑内CB表达较多,AQP4表达较少,脑含水量较低。结论阻断腺苷A2A受体对脑缺血急性期和再灌注期损伤均有保护作用,并减轻缺血引起的脑水肿,可能与抑制细胞内钙超载和AQP4的表达有关。Objective To investigate the effect of adenosine A2A receptor deficiency on the ischemic neuronal injury and its potential mechanism. Methods Transient （2 h） cerebral ischemia was induced by the middle cerebral artery occlusion （MCAO） in mice. Adenosine A2Areceptor knockout （A2ARKO） mice and their wild-type littermates （AzARWT） were divided into 2-hour cerebral ischemia group, cerebral ischemia with 22- hour reperfusion group and cerebral ischemia with 46-hour reperfusion group. Cerebral infarction volume was measured by image analysis of brain sections stained with cresyl violet （CV）. Brain water content was evaluated with the dry-wet weighing method. The expression of calbindin D-28k （CB） and aquaporin-4 （AQP4） in ischemic brain was determined with immunohistochemical methods. Results The cerebral infarction volumes in 2- hour cerebral ischemia group, cerebral ischemia with 22-hour reperfusion group and cerebral ischemia with 46- hour reperfusion group of A2ARKO mice were lesser than those in the corresponding groups of AzARWT mice. Compared with A2ARWT mice, A2ARKO mice had more CB, lesser AQP4 expressions and lesser brain water contents. Conclusion Adenosine A2Areceptor deficiency exerts the protection against ischemic brain injury both in the acute phase and reperfusion phase, and attenuates brain edema caused by cerebral isehemia, which may be due to the inhibition of intracellular calcium overload and AQP4 expression.

关 键 词：腺苷 A2A受体 基因敲除 大脑中动脉局灶缺血 损伤 

分 类 号：R394.1[医药卫生—医学遗传学] R741.02[医药卫生—基础医学]