摘要
目的探讨在不同A1受体活性状态下,腺苷A2A受体缺失对脑缺血/再灌注区GLT-1D的影响,并探讨其产生的缺血性脑保护的可能机制。方法将腺苷A2A受体基因敲除小鼠(A2AR/KO)与野生型小鼠(A2AR/WT)制作成大脑中动脉缺血2 h/再灌注22 h模型,分别给予腺苷A1受体激动剂CPA及拮抗剂DPCPX,采用免疫组化、Western-blot方法检测缺血/再灌注区(纹状体区)谷氨酸转运体(GLT-1)的表达情况,同时观察对脑梗死体积和神经功能缺损程度的影响。结果缺血2h/再灌注22 h后,KO小鼠的神经功能缺损程度均明显轻于同样干预的WT小鼠(P<0.05),使用A1受体拮抗剂后,小鼠的神经缺损程度较非干预组明显加重,而使用A1受体激动剂后神经功能缺损程度较非干预组明显减轻;KO小鼠的梗死体积均明显小于同样干预的WT小鼠(P<0.01),A2AR-KO/A1拮抗剂组小鼠梗死体积较非干预小鼠明显增大,而A2AR-KO/A1激动剂组小鼠的梗死体积则明显缩小。在缺血/再灌注区,A1R激动剂CPA使小鼠的GLT-1表达明显高于非干预组,其中A2AR/KO小鼠的增加更为明显;而使用A1R拮抗剂DPCPX后,局部GLT-1的表达与非干预组相比无明显差异。结论初步证明A2AR缺失产生的神经保护作用与A1受体功能激活,进而促进缺血/再灌注区GLT-1的表达增加有关。抑制A2AR,同时激活A1R能加强缺血性脑保护作用。
Objective To investigate the effect of adenosine A2A receptor deficiency in different A1 receptor activities on the ischemic neuronal injury and its potential mechanism of ischemic neuroprotection.Methods MCAO/reperfusion model was created in A2 Areceptor knock-out（KO） mice and wild type（WT） was used for controls.These mice were divided into three groups： non-treatment group,A1 receptor activator treatment group,and A1 antagonist treatment group.The expression of GLT-1 was observed in adenosine A2 Areceptor deficiency on the ischemic neuronal injury by immunohistochemical methods,RT-PCR and Western-Blot.The cerebral infarction volume and the neurological deficit condition were also observed.Results The neurological deficit scores in the cerebral ischemia（2 h）/reperfusion（22 h） were remarkably lower in KOmice than in WT mice（P〈0.05）.In the A1 antagonist treatment group,the neurological deficit scores were remarkably higher than those without any drug intervention in both KOand WT mice.In the presence of A1 receptor stimulator,the neurological deficit scores were remarkably lower than those without any drug intervention in both KO and WT mice.There was more cerebal infarction volume of A2 AR-KO in antagonist treatment group than in non-treatment group.However,there was less cerebal infarction volume of A2 AR-KO in activator treatment group than in other groups.The expression of GLT-1 in the striatum region was significantly higher in KO mice than in WT mice.And the expression of GLT-1 was also higher in A2 AR-WT antagonist treatment group.Conclusion The preliminary study shows that the neuroprotection from knock-out A2 Areceptor in ischemic condition can enhance the expression of GLT-1,refrain A2 AR and activate A1 R to increase protection.
出处
《实用临床医药杂志》
CAS
2012年第3期1-5,9,共6页
Journal of Clinical Medicine in Practice
基金
国家自然科学基金项目(30800354)
关键词
脑梗死
腺苷受体
大脑中动脉
栓塞
谷氨酸转运体
cerebral infarct； adenosine receptor； middle cerebral artery occlusion（MCAo）； glutamate transporter；
