Ro25-6981对成年脑缺血-再灌注大鼠海马CA1区神经发生影响.docVIP

Ro25-6981对成年脑缺血/再灌注大鼠海马CA1区神经发生影响 　 作者：王姗姗，胡忠浩，徐铁军 【摘要】 目的 探讨NMDA受体亚单位2B选择性拮抗剂Ro25-6981对成年大鼠短暂性全脑缺血再灌注后海马CA1区神经发生的影响。方法 将成年雄性SD大鼠随机分为实验组和对照组。制作四动脉阻断(4AO)大鼠全脑缺血15 min再灌注模型。实验组和对照组大鼠分别于术前30 min腹腔注射不同剂量Ro25-6981(0.3 mg/kg、0.6 mg/kg)、生理盐水。免疫组织化学技术显示再灌注第1、3、7天各组大鼠海马CA1区BrdU阳性细胞数。结果 对照组大鼠BrdU阳性细胞在再灌注3 d增殖达高峰，随后下降。 再灌注1、3、7天，实验组与对照组相比BrdU阳性细胞数均明显减少(Plt;0.01)。结论 一定条件下，Ro25-6981可抑制缺血再灌注诱导的海马CA1区的短暂性神经发生。 【关键词】 脑缺血/再灌注;NMDA受体拮抗剂;神经发生;大鼠 　　Abstract: Objective To investigate the effect of the selective antagonist Ro25-6981 of NMDA receptor subunit 2B (NR2B) on the neural recovery in adult rat hippocampus after transient forebrain ischemia/reperfusion (I/R). Methods The male SD rats were randomized into three groups: the experiment groups (Ⅰand Ⅱ) and the control group. The rats in the experiment groups and the control group were subjected to 15 min of 4-artery occlusion (4AO) to establish the animal model of rat brain ischemia (15 min) and reperfusion. The rats in the experiment groups were intraperitoneally administered with Ro25-6981 at doses of 0.3 mg/kg and 0.6 mg/kg, respectively, while the same volume of NS was injected into the rats in the control group. Immunohistochemistry was employed to demonstrate and to compare the rate of BrdU positive cells in CA1 of hippocampus in different groups at 1 d, 3 d and 7 d. Results The control group: BrdU positive cells peaked at I/R 3 d and decreased until I/R 7 d in the CA1 region. The experiment groups: The numbers of BrdU-positive cells significantly decreased as compared to that in the control group. Conclusion Transient forebrain ischemia/reperfusion could induce neurogenesis in the CA1 region, while this kind of neurogenesis could be inhibited by Ro25-6981. 　　Key words: ischemia/reperfusion; NMDA receptor antagonist; neurogenesis 　　缺血性脑血管病是严重威胁人类健康的常见病和多发病。目前认为，当发生缺血缺氧时，刺激谷氨酸受体，尤其是引起NMDAR过度兴奋，导致神经细胞Ca2+超载而致损伤[1]。于是人们试图使用NMDAR拮抗剂缓解脑缺血引起的神经细胞死亡。 　　有研究表明NMDAR拮抗剂MK-801可刺激正常的成年大脑神经发生[2-3]。注射MK-801虽然可以防止短暂性局脑缺血后海马CA1区神经元的死亡，但同时也阻止了海