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目的研究N-甲基-D-天冬氨酸(NMDA)受体拮抗剂MK-801对新生7 d大鼠室管膜下区(SVZ)胶质纤维酸性蛋白(GFAP)表达的影响。方法将40只新生SD大鼠分成对照组和MK-801组,各组按出生后(P)时间点再随机分成4个亚组:P7 d、P14 d、P21 d、P28 d组。新生大鼠均于生后第3天给药,MK-801组腹腔注射MK-801 10 mg.kg-1;对照组腹腔注射同量生理盐水。通过免疫组化学方法观察大鼠SVZ区GFAP阳性细胞数。结果①对照组GFAP阳性细胞数于P14 d开始增加,至P21 d达最大值;但P28 d时阳性细胞迅速下降;②MK-801组GFAP阳性细胞数与对照组相比,P7 d和P28 d无明显差异,P14 d(65.40±6.11)和P21 d(239.60±12.92)细胞数明显减少;而对照组P14 d(79.20±5.26)、P21 d(265.20±7.40)GFAP阳性细胞数明显增多,差异有显著统计学意义(P<0.01)。结论 NMDA受体拮抗剂MK-801对正常新生大鼠SVZ区GFAP的表达有抑制作用,能够抑制SVZ区神经干细胞的增殖和分化。
Objective To investigate the effect of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, on glial fibrillary acidic protein (GFAP) expression in subventricular zone (SVZ) of neonatal rats. Methods 40 neonatal SD rats were divided into control group and MK-801 group. Each group was randomly divided into 4 subgroups according to postnatal (P) time points: P7 d, P14 d, P21 d and P28 d groups. Neonatal rats were administered on the third day after birth. MK-801 group was injected intraperitoneally with MK-801 10 mg.kg-1. The control group was intraperitoneally injected with the same amount of saline. Immunohistochemistry was used to observe the number of GFAP positive cells in SVZ of rats. Results ① The number of GFAP positive cells in control group began to increase from P14 d to the maximum on P21 d, but decreased rapidly on P28 d. ② The number of GFAP positive cells in MK-801 group was significantly higher than that in control group, P7 d and P28 d (P <0.01). The number of GFAP positive cells on P14d (79.20 ± 5.26) and P21d (265.20 ± 7.40) in P14d (65.40 ± 6.11) and P21d (239.60 ± 12.92) significantly decreased in control group Significant statistical significance (P <0.01). Conclusion NMDA receptor antagonist MK-801 can inhibit the expression of GFAP in SVZ of normal neonatal rats, which can inhibit the proliferation and differentiation of neural stem cells in SVZ.