摘要
目的:研究N-甲基-D-天冬氨酸受体(NMDAR)亚单位2B(NR2B)特异性拮抗剂(Ro 25-6981)对缺氧缺血性脑损伤(HIBD)新生大鼠脑室下区(SVZ)神经干细胞(NSCs)增殖的影响。方法:7 d龄新生SD大鼠随机分为Ro 25-6981组(HIBD前2 h,腹腔注射Ro 25-6981 10 mg.kg-1)、HIBD组(HIBD前2 h,腹腔注射等剂量生理盐水)和假手术组(仅游离右侧颈总动脉,不结扎)。采用免疫组化学染色检测SVZ Nestin表达量及BrdU阳性细胞数的变化。结果:HIBD组12h后Nestin表达量开始增多,48 h达峰值,之后缓慢下降;与其相比,Ro 25-6981组在12 h和24 h时下降明显(P<0.05)。HIBD组BrdU阳性细胞数在缺氧缺血3 h后缓慢上升,72 h达高峰;与其相比,Ro 25-6981组在各时间点BrdU阳性细胞表达均有所下降,以24、48和72 h减少明显,尤以72 h为著(P<0.05)。结论:Ro 25-6981能够降低HIBD新生大鼠SVZ Nestin的表达及Brdu阳性细胞数,对SVZ NSCs增殖起抑制作用,提示NR2B参与并促进HIBD引起的SVZ NSCs的增殖。
Aim： To investigate the effect of N-methyl-D-aspartic acid receptor （NMDAR） subunit 2B antagonist on the proliferation of neural stem cells （NSC） in the subventricular zone（SVZ） of the hypoxic- ischemic brain damage（HIBD） neonatal rats. Methods： The neonatal Sprague-Dawley rats aged 7 d were randomly divided into three groups： Ro 25-6981 group, sham-surgery control group and HIBD group. Ro 25- 6981 （10 mg-kg-1, ip） and the same amount of normal saline were injected intra-peritoneally into Ro 25-6981 intervened group and HIBD group respectively 2 h before hypoxic-ischemic （HI） insult. The expression of SVZ Nestin and BrdU positive cells in all groups were detected by immunohistochemical staining. Results： ~） In HIBD group, the expression of Nestin positive ceils gradually increased after 12 h and had a peak at 48 h, and then declined. While in Ro 25-6981 group, the expression of Nestin positive cells declined significantly after 12 h and 24 h（P〈0.05）. ~ After hypoxic-ischemic brain damage, BrdU positive cells proliferated at 3 h and had a peak at 72 h, and then declined in HIBD group, but fewer in Ro 25-6981 group at all time points, especially at 24 h, 48 h and 72 h, significantly at 72 h（P〈0.05）. Conclusion： Ro 25-6981 can inhibit the proliferation of the NSCs induced by HIBD in SVZ, which suggested that NR2B mediate and promote the proliferation of NSCs after HIBD in the subventricular zone.
出处
《中国临床神经科学》
2012年第6期614-618,共5页
Chinese Journal of Clinical Neurosciences
基金
国家自然科学基金项目(编号:81171141)
