目的:研究Ro25-6981对成年大鼠短暂性脑缺血再灌注海马齿状回颗粒下层(subgranular zone,SGZ)神经干细胞增殖的影响。方法:健康成年雄性SD大鼠在进行侧脑室置管7 d后,随机分为正常组、假手术组和脑缺血再灌注组,每组又分别再分为Ro25-6981组和生理盐水组。缺血再灌注组大鼠采用四动脉阻断前脑缺血再灌注模型,即缺血15 min再灌注1、3、7、14、21、28 d和35 d,缺血前15 min经侧脑室套管注射Ro25-6981或生理盐水。各组大鼠均采用免疫组织化学显示SGZ区Brd U、nestin阳性细胞的表达情况,采用免疫荧光双重标记法检测再灌7 d时SGZ区Brd U/nestin双标阳性细胞数量的改变。结果:脑缺血再灌注生理盐水组SGZ区nestin阳性细胞表达再灌1 d时开始增多,7 d时达到峰值,14 d时急剧下降,至35 d时降至正常水平;缺血前给予Ro25-6981,各时间点的nestin阳性细胞表达均有所下降,其中在3、7 d和14 d时减少明显,差异有统计学意义(P<0.05)。脑缺血再灌注生理盐水组SGZ区Brd U阳性细胞再灌1 d开始增殖,7 d达到峰值,35 d降至正常水平;缺血前给予Ro25-6981,各时间点的Brd U阳性细胞表达均有所下降,其中在3、7、14 d和21 d时减少明显,差异有统计学意义(P<0.05)。与脑缺血再灌注生理盐水组相比,Ro25-6981可以降低脑缺血再灌7 d海马SGZ区的Brd U/nestin双标阳性细胞密度,差异有统计学意义(P<0.05)。结论:Ro25-6981可以抑制前脑缺血再灌注后海马SGZ区神经干细胞的增殖,提示NR2B参与并促进了前脑缺血再灌注引起的神经干细胞的增殖。 Objective: To investigate the effect of Ro25-6981 on the proliferation of neural stem cells in the subgranular zone of the dentate gyrus of adult rats with transient cerebral ischemia / reperfusion. Methods: Healthy adult male Sprague - Dawley rats were randomly divided into normal group, sham operation group and cerebral ischemia reperfusion group after 7 d of lateral ventricular catheterization. Each group was divided into Ro25-6981 group and normal saline group . The ischemia-reperfusion rats were blocked by four-artery occlusion model of forebrain ischemia-reperfusion, that is, ischemia reperfusion 15 min, reperfusion 1, 3, 7, 14, 21, 28 and 35 d, Intracerebroventricular cannula injection Ro25-6981 or saline. Immunohistochemistry was used to detect the expression of BrdU and nestin positive cells in SGZ, and the number of BrdU / nestin double positive cells in SGZ was detected by immunofluorescence double labeling method. Results: The expression of nestin positive cells in SGZ of ischemic reperfusion group began to increase at 1 day of reperfusion, reached its peak at 7 days and decreased sharply at 14 days, then decreased to normal level at 35 days. Ro25 -6981. The expression of nestin positive cells decreased at each time point, which decreased significantly at 3, 7 and 14 d (P <0.05). BrdU positive cells in the SGZ of cerebral ischemia-reperfusion group began to proliferate on the 1st day after reperfusion, reached the peak on the 7th day and dropped to the normal level on the 35th day; Ro25-6981 was given before ischemia, BrdU positive cells were expressed at each time point Decreased at 3, 7, 14 and 21 d, respectively, with significant difference (P <0.05). Compared with NS group, Ro25-6981 could reduce the density of BrdU / nestin double positive cells in SGZ of hippocampus on the 7th day after cerebral ischemia-reperfusion, with statistical significance (P <0.05). CONCLUSION: Ro25-6981 can inhibit the proliferation of neural stem cells in SGZ of hippocampus after forebrain ischemia-reperfusion, suggesting that NR2B is involved in and promotes the proliferation of neural stem cells induced by forebrain ischemia-reperfusion.