文档介绍：γ-氨基丁酸A受体在大鼠急性脑缺血中的变化
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作者:孙智敏张茂林张俊清薛继娇
【摘要】目的:观察大鼠大脑皮质γ-氨基丁酸A受体(γ-aminobutyric acid A receptors,GABAAR)在脑缺血不同时段的表达及其动态变化的规律,探讨其在急性脑缺血中变化的意义。方法:65只雄性Wistar大鼠随机分为对照组,脑缺血6 h组、12 h组、24 h组、3 d组、7 d组、14 d组(均为手术组),假手术组;采用大鼠大脑中动脉栓塞(MCAO)模型,至规定时间点取大脑组织,行HE染色,用光学显微镜观察神经元损伤程度;用免疫组织化学技术判断神经元阳性表达的强弱;用形态分析系统检测各组GABAAR表达的阳性细胞数。结果:各手术组GABAAR表达均低于假手术组及对照组,与对照组相比,缺血6 h其表达既有降低,至12 h降至最低。而假手术组与对照组相比无统计学意义。结论:急性脑缺血可引起GABAAR表达下调,致使其对兴奋性氨基酸毒性的抑制作用减弱,这种下调和减弱程度与脑缺血的严重程度相一致,提示GABAAR在缺血性脑损伤中有神经保护作用,可能减缓了缺血性脑血管病的进程,同时GABAAR作为脑内最主要的一种抑制性氨基酸神经递质受体,除通过其配体门控性Cl-通道介导的效应对抗“兴奋毒性”作用外,GABAAR本身也因缺血所致理化因素的改变而发生变化。
【关键词】脑缺血;γ-氨基丁酸A受体;大鼠
Abstract Objecive: To observe the expression of GABAAR and the dynamic regulation in the cortex of rats with focal cerebral ischemia in different phases and to investigate its significance in acute ischemia. Methods: Forty-eight male Wistar rats were randomly divided into 13 groups: The normal control, sham operation and ischemic operation group(subdivided into 6,12,24 hour and 3,7,14 days) by middle cerebral artery occlusion model. Brain specimens of the rats from each group were obtained for HE staining to observe the damage of neurons with light microscope and to judge the positive expression of neurons in immunohistochemistry technique, and then to determine the positive cell number expressed by GABAAR in each group with morphologic analysis system. Results: Compared with the normal control group and the sham operation group, the expression of GABAAR in each ischemia operation group was decreased 6h after ischemia and reached the bottom within 12 hours after ischemia. However, there was no significant difference between the normal control group and sham operation group. Conclusion: Acute cerebral ischemia can cause down-regulated expression of GABAAR and weaken its inhibitory action on glutamate excitotoxicity, which is accordant with the degree of cerebral ischemia injury, which suggests that GABAAR plays a role of