MK-801对局灶性脑缺血再灌注大鼠细胞增殖的影响

Effect of MK-801 on cell proliferation following focal cerebral ischemia reperfusion in rats

目的研究MK-801对局灶性脑缺血再灌注大鼠神经干细胞增殖的影响。方法60只雄性SD大鼠,随机分为正常对照组(n=6)、假手术组(n=6)、手术组(n=12)和手术MK-801不同浓度干预组(0.2、0.4、0.6、0.8、1.0和1.2mg/kgn=36)。用线栓法建立大脑中动脉缺血再灌注模型,在模型制作前30min按照不同浓度组的剂量腹腔注射MK-801,假手术组和手术对照组腹腔注射等量的生理盐水。在模型建立后第7天,通过免疫组化技术标记大鼠梗塞区大脑皮质的Brdu阳性细胞数目。结果MK-801浓度为0.4mg/kg时,可以明显抑制内源性神经干细胞的增殖,0.8mg/kg剂量以上有显著的抑制作用,并且随着浓度升高抑制作用呈递增趋势。结论NMDA受体拮抗剂MK-801在局灶性脑缺血后对大鼠内源性神经干细胞的增殖有抑制作用,并且随浓度的增加抑制作用增强。

[Objective] To study the effect of MK-801 on neural stem cell proliferation of focal cerebral ischemia reperfusion in rats. [Methods] The sixty male SD rats were randomly divided into three groups, the normal contral group （n =6）, the sham operation group（n =6）, the opertaion group（n =12） and the operation with different MK-801 dose interfering group （0.2, 0.4, 0.6, 0.8, 1.0 and 1.2 mg/kg, n =36）. The animal model of brain medium-sized artery focal cerebral ischemia reperfusion with the patehing methods, the different dose of MK-801 were intraperitoneal in- jected 30 minutes before the anminal model building, while the sham operation group and the operation eontrol group were intmperitoneal injected the same dose Sodium Chloride. The brain mantle Brdu positive eell were marked with the immune histoehemistry method in area of block after the model building. [Result] At the dose of 0.4 nag/ Kg, MK-801 ean obviously inhibit the proliferation of endogenous neural stem cell, beyond the dose of there was sig- nificant inhibitory action. What＇s more, followed the dose of MK-801 increasing, the inhibitory aefion has a conspic- uous tendency of decreasing progressively. [Conclusion] The NMDA receptor antagon MK-801 ean inhibit the proliferation of endogenous neural stem cell and the inhibitory action beeomes stronger with the dose increasing.