CAJ | 학술논문

目的：探讨新生期重复注射N-甲基-D-天冬氨酸（N-methyl-D-aspartate，NMDA）受体拮抗剂地卓西平马来酸盐（dizocilpine maleate，MK-801）对不同发育阶段大鼠NMDA受体亚基NMDAR1（NR1）、NMDAR2A （NR2A）、NMDAR2B（NR2B）表达及神经生长因子（nerve growth factor，NGF）含量的影响。方法30只新生雄性大鼠随机分为研究组和对照组，各15只。于出生后（postnatal day，PND）5~14d皮下注射MK-801（0.25mg/kg，每日2次）或生理盐水。分别于幼年期（PND15）、青春期（PND42）和成年期（PND70）取脑留取海马、前额叶皮质脑区，用免疫印迹（Western blot）方法检测NR1、NR2A、NR2B表达水平，用ELISA方法测定NGF含量。结果幼年期（PND15）与对照组相比，研究组海马与前额叶NMDA受体各亚基表达水平及NGF含量没有统计学差异（均P>0.05）；青春期（PND42）研究组大鼠前额叶NGF含量低于对照组[（56.19±37.87）vs.（152.54±53.92）]，差异有统计学意义（P<0.01）；成年期（PND70）研究组大鼠海马NR1、NR2A表达水平较对照组增加[NR1：（149.55%±27.00%）vs.（100.00%±32.08%）；NR2A：（171.54%±19.85%）vs.（100.00%±51.04%）]，差异均有统计学意义（均P<0.05）。结论新生期重复注射MK-801选择性上调成年大鼠海马NMDA受体亚基NR1和NR2A的表达水平，且显著降低青春期大鼠前额叶NGF的含量。提示发育早期阻断NMDA受体对大鼠大脑的神经发育产生远期影响。
목적：탐토신생기중복주사N-갑기-D-천동안산（N-methyl-D-aspartate，NMDA）수체길항제지탁서평마래산염（dizocilpine maleate，MK-801）대불동발육계단대서NMDA수체아기NMDAR1（NR1）、NMDAR2A （NR2A）、NMDAR2B（NR2B）표체급신경생장인자（nerve growth factor，NGF）함량적영향。방법30지신생웅성대서수궤분위연구조화대조조，각15지。우출생후（postnatal day，PND）5~14d피하주사MK-801（0.25mg/kg，매일2차）혹생리염수。분별우유년기（PND15）、청춘기（PND42）화성년기（PND70）취뇌류취해마、전액협피질뇌구，용면역인적（Western blot）방법검측NR1、NR2A、NR2B표체수평，용ELISA방법측정NGF함량。결과유년기（PND15）여대조조상비，연구조해마여전액협NMDA수체각아기표체수평급NGF함량몰유통계학차이（균P>0.05）；청춘기（PND42）연구조대서전액협NGF함량저우대조조[（56.19±37.87）vs.（152.54±53.92）]，차이유통계학의의（P<0.01）；성년기（PND70）연구조대서해마NR1、NR2A표체수평교대조조증가[NR1：（149.55%±27.00%）vs.（100.00%±32.08%）；NR2A：（171.54%±19.85%）vs.（100.00%±51.04%）]，차이균유통계학의의（균P<0.05）。결론신생기중복주사MK-801선택성상조성년대서해마NMDA수체아기NR1화NR2A적표체수평，차현저강저청춘기대서전액협NGF적함량。제시발육조기조단NMDA수체대대서대뇌적신경발육산생원기영향。
Objective To investigate the effects of repeated neonatal administration of dizocipline maleate (MK-801), the N-methyl-D-aspartate (NMDA) receptor antagonist, on the expression of NMDA receptor subunits NMDAR 1 (NR1), NMDAR2A (NR2A), NMDAR2B (NR2B) and the protein levels of nerve growth factor (NGF) in neonatal rats. Methods Neonatal Sprague-Dawley (SD) rats were randomly divided into research group and control group, with 15 ani-mals in each group. Rats were administrated subcutaneously with MK-801 or normal saline from postnatal day (PND) 5 to PND14 (0.25 mg/kg, twice a day). The expression levels of NR1, NR2A, NR2B and NGF were examined on PND15, PND42 and PND70 in the prefrontal cortex and hippocampus. Results At PND15 (neonatal period), there were no signifi-cant differences in the expression levels of NR1, NR2A, NR2B and NGF in the prefrontal cortex and hippocampus be- tween the two groups (P>0.05). At PND42 (adolescence), NGF protein levels in the prefrontal cortex was significantly low-er in research group than in control group [(56.19±37.87) vs. (152.54±53.92), P<0.01]. At PND70 (adulthood), the expres-sion of NR1, NR2A in the hippocampus was significantly higher in research group than in control group [NR1:(149.55%± 27.00%) vs. (100.00%±32.08%);NR2A:(171.54%±19.85%) vs. (100.00%±51.04%). P<0.05]. Conclusion Neonatal re-peated treatment of MK-801 increases the expression of NMDA receptor subunits NR1, NR2A in the hippocampus in adulthood while decreases the expression of NGF in the prefrontal cortex in adolescence, suggesting that neonatal block-ade of the NMDA receptor may influence the growth and development of the nervous system.