阻断腺苷A2a受体对大鼠大脑中动脉缺血再灌注损伤区谷氨酸转运体GLT-1表达的影响

Influence of adenosine receptor A2a antagonist on glutamate transporter GLT-1 expression in middle cerebral artery ischemia-reperfusion injury zone of rats

目的观察腺苷受体A2 a拮抗剂对大鼠MCAO模型纹状体中谷氨酸转运体GLT-1表达的影响,并探讨其对缺血性神经保护作用的机制。方法分别在雄性SD大鼠脑缺血2 h、缺血2 h再灌注22 h给予腺苷受体A2 a拮抗剂SCH-58261,采用RT-PCR、WB方法检测纹状体区GLT-1的表达,同时观察脑梗死体积和神经功能缺损情况。结果缺血2 h组的神经功能评分无明显差异;缺血2 h再灌注22 h干预组神经功能评分(1.67±0.52)与对照组(2.50±0.55)比较,有显著差异(P<0.05);缺血2 h干预组梗死体积(23.63±3.89),比对照组缩小了16%(P<0.05)。缺血2 h再灌注22 h干预组梗死体积(95.12±18.22),比对照组缩小了33%(P<0.01);给予SCH-58261后,MCAO大鼠在急性缺血期和缺血再灌注期纹状体中GLT-1表达均明显增高。结论初步证明阻断腺苷受体A2 a对脑缺血产生的保护作用与增强了GLT-1的功能有关。

Objective To observe the influence of adenosine receptor A2a antagonist on the glutamate transporter GLT-1 expression in the corpus striatum of rat middle cerebral artery occlusion（MCAO） models,and investigate its mechanism of ischemic neuroprotection.Methods Two models of male SD rats,one suffering 2 h of cerebral ischemia and the other suffering 2 h of cerebral ischemia followed by 22 h of reperfusion,were constructed.Each model was divided in a sham operation group,an ischemia control group,and an intervention group.Adenosine receptor A2a antagonist SCH-58261 was administered to the sham operation groups and the intervention groups.The expression of GLT-1 in the corpus striatum was detected by RT-PCR and Western blotting.The cerebral infarction volume and the neurological deficit condition were also observed.Results There was no significant difference between the neurological deficit scores of the control group and the intervention group in the cerebral ischemia（2 h） model.There was a significant difference between the neurological deficit scores of the control group（2.50±0.55） and the intervention group（1.67±0.52） in the cerebral ischemia（2 h）-reperfusion（22 h） model（P0.05）.The cerebral infarction volume（23.63±3.89） of the intervention group in the cerebral ischemia（2 h） model was decreased by 16%（P0.05） as compared to that of the control group.The cerebral infarction volume（95.12±18.22） of the intervention group in the cerebral ischemia（2 h）-reperfusion（22 h） model was decreased by 33%（P0.01） as compared to that of the control group.After SCH-58261 administration,the expression of GLT-1 in the corpus striatum of rat MCAO models during the acute ischemia stage and the ischemia-reperfusion stage was increased significantly.Conclusion The neuroprotection of adenosine receptor A2a antagonist against cerebral ischemia is correlated with the enhancement of GLT-1 function.