右美托咪定预处理抑制脑缺血再灌注时谷氨酸的释放及其受体机制研究
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高光洁,E-mail:guangjie420@126.com,Tel:024-28845351

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辽宁省自然科学基金资助项目(No:2015020416)


Dexmedetomidine inhibit Glu release and NR1 expression in hippocampus on global cerebral ischemia-reperfusion rats
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    摘要:

    目的  评价右美托咪定预处理对大鼠全脑缺血再灌注损伤时海马谷氨酸(Glu)及其受体NMDAR1(NR1)表达的影响。方法  雄性Wistar大鼠90只,体重250~300 g,采用随机数字表法,将其分为3组(n =30):假手术组(S组)、全脑缺血再灌注组(I/R组)和右美托咪定组(D组),采用四血管阻断法制备全脑缺血再灌注损伤模型。D组于全脑缺血前2 h经尾静脉注射右美托咪定3μg/kg,随后以3μg/(kg·h)速率输注120 min,I/R组给予等容量生理盐水。应用Combs评分系统评价大鼠神经运动功能的缺损情况;采用脑微透析技术结合高效液相色谱(HPLC)检测大鼠海马细胞外Glu水平的变化;采用免疫组织化学方法检测海马CA1区NR1蛋白表达。结果  与S组比较,I/R组和D组大鼠平衡木和引绳肌力试验评分下降(P <0.05),海马细胞外Glu的水平增高(P <0.05),海马CA1区NR1表达上调(P <0.05);与I/R组比较,D组大鼠平衡木和引绳肌力试验评分升高(P <0.05),海马细胞外Glu的水平降低(P <0.05),海马CA1区NR1表达下调(P <0.05)。 结论 右美托咪定可减轻大鼠全脑缺血再灌注损伤,改善神经运动功能的缺损,其机制与抑制Glu释放和下调NR1表达有关。

    Abstract:

    Objective To investigate the effect of Dexmedetomidine on glutamate (Glu) release and NR1 expression in hippocampus on global cerebral ischemia-reperfusion rats. Methods Ninety male Wistar rats were randomly divided into three groups; group S received sham operation; group I/R received ischemia-reperfusion; group D received Dexmedetomidine treatment before ischemia-reperfusion (n = 30). Global cerebral ischemia was induced according to Pulsinelli-Brierley method. In group D, Dexmedetomidine 3 μg/kg was injected through tail vein before ischemia, then 3 μg/(kg·h) with injection pump. Meanwhile equal volume saline administrated in group I/R animals. Combs was used to evaluate nerve function of rats; Glu levels were detected by HPLC in the rat hippocampus; NR1 expression in CA1 area was detected by immunohistochemistry method. Results Compared with group S, Balance beam and rope strength test scores in group I/R and D were significant decrease (P < 0.05), and the level of Glu and NR1 were increase significantly (P < 0.05). Compared with group I/R, Balance beam and rope strength test scores in group D were significant decreased (P < 0.05), and the level of Glu and NR1 were increased significantly (P < 0.05). Conclusion Dexmedetomidine can reduce the rat global cerebral ischemia reperfusion injury and improve the nerve function defect, and the mechanism is related to the inhibition of Glu release and down regulate NR1 expression.

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尚宇,关双成,李悦,高光洁.右美托咪定预处理抑制脑缺血再灌注时谷氨酸的释放及其受体机制研究[J].中国现代医学杂志,2016,(4):1-4

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  • 收稿日期:2015-09-16
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  • 在线发布日期: 2016-02-29
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