[1]祝　伟　孔　伟　李　拓　陈鸿光　汤国太.幼鼠癫痫模型海马神经元NMDA受体表达与MMP-3表达相关性[J].中国临床神经外科杂志,2018,(02):99-102.
　ZHU Wei,KONG Wei,LI Tuo,et al.Relativity of NMDA receptor with MMP-3 expression in hippocampal neurons in juvenile mice with epilepsy[J].,2018,(02):99-102.
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幼鼠癫痫模型海马神经元NMDA受体表达与MMP-3表达相关性 ()

《中国临床神经外科杂志》[ISSN:1009-153X/CN:42-1603/TN]

卷:
期数:
2018年02期
页码:
99-102
栏目:
论著
出版日期:
2018-03-05

文章信息/Info

Title:
Relativity of NMDA receptor with MMP-3 expression in hippocampal neurons in juvenile mice with epilepsy
文章编号:
1009-153X（2018）02-0099-04
作者:
祝　伟　孔　伟　李　拓　陈鸿光　汤国太
作者单位：264000 山东，烟台毓璜顶医院神经外科（祝　伟、孔　伟、李　拓、陈鸿光、汤国太）
Author(s):
ZHU Wei;  KONG Wei;  LI Tuo;  CHEN Hong-guang;  TANG Guo-tai.
Department of Neurosurgery, Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai 264000, China
关键词:
癫痫模型; 幼鼠; N-甲基-D-天冬氨酸受体; 基质金属蛋白酶-3; 基因表达
Keywords:
Epilepsy;  Juvenile mice;  NMDA receptors;  MMP-3;  P-gp;  CAMKⅡ
分类号:
R 742.7; Q 786
文献标志码:
A
摘要:
目的 探讨幼鼠癫痫模型海马神经元N-甲基-D-天冬氨酸受体（NMDAR）表达与基质金属蛋白酶-3（MMP-3）表达的相关性。方法 将60只2~4周龄SPF级C57/BL6小鼠随机分为正常组、癫痫组、MMP-3抑制剂组、NMDAR抑制剂组，每组15只。采用匹罗卡品建立幼鼠癫痫模型；采用RT-PCR检测海马神经元NMDAR2A、NMDAR2B、MMP-3 mRNA表达；采用尼氏染色观察海马区神经元形态；采用Western blot检测海马区P-糖蛋白（P-gp）、钙调蛋白激酶Ⅱ（CAMKⅡ）蛋白表达。结果 幼鼠癫痫模型海马区NMDAR2A/B、MMP-3 mRNA以及P-gp、CAMKⅡ蛋白较正常组显著增加（P<0.05）。注射NMDA受体抑制剂或MMP-3抑制剂可显著降低幼鼠癫痫模型NMDAR2A/B、MMP-3 mRNA及P-gp、CAMKⅡ蛋白表达，且明显改善海马区神经元结构。结论 幼鼠癫痫模型海马神经元MMP-3表达与MNDAR表达可能具有相关性。
Abstract:
Objective To explore the relativity of N-methyl-D-aspartic acid (NMDA) receptors with Matrix metalloproteinases-3 (MMP-3) expression in hippocampal neurons in juvenile mice with epilepsy. Methods Sixty juvenile mice were divided into 4 groups of 15 animals each, including control, epilepsy model, NMDA receptor (NMDAR) 2A, B inhibitor and MMP-3 inhibitor groups. The epilepsy model was established in all the groups except the control group. The expressions of NMDAR 2A, and MMP-3 RNA in the hippocampal tissues were detected by RT-PCR in all the groups. The morphology of hippocampal neurons was observed by Nissl staining in all the groups. The expressions of P-glycoprotein (P-gp) and Calmodulin kinase Ⅱ (CAMK Ⅱ) proteins in the hippocampal tissues were detected by Western blot in all the groups. Results The levels of the expressions of NMDAR2A, B and MMP-3 mRNA P-gp and CAMK Ⅱ in the hippocampus tissues were significantly higher in the epilepsy model group than those in the control group (P<0.05). The levels of NMDAR2A, B and MMP-3 mRNA, and P-gp and CAMK Ⅱ in the hippocampal tissues were significantly lower in NMDAR2A, B inhibitor and MMP-3 inhibitors groups than those in the epilepsy model group (P<0.05). The structures in the hippocampal neurons were significantly improved in the NMDAR2A, B inhibitor and MMP-3 inhibitor groups compared with those in the epilepsy model group. Conclusions The expression of MMP-3 may be positively related to the expression of NMDAR in the hippocampal tissues in the juvenile mice with epilepsy.

参考文献/References:

[1] 叶建林，徐晓华，洪　荣，等. 不同发育阶段儿童癫痫的用 药特点及不良反应研究进展[J]. 中国临床药理学杂志， 2015，31（2）：155-157.
[2] Miyamoto T, Stein L, Thomas R, et al. Phosphorylation of tau at Y18, but not taufyn binding, is required for tau to modulate NMDA receptor-dependent excitotoxicity in primary neuronal culture [J]. Mol Neurodegener, 2017, 12: 41-60.
[3] Addis L, Virdee JK, Vidler LR, et al. Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency-molecular profiling and functional rescue [J]. Sci Rep, 2017, 2(7): 66-90.
[4] Huntley GW. Synaptic circuit remodelling by matrix metal- loproteinases in health and disease [J]. Nat Rev Neurosci, 2012, 13(11):743-757.
[5] Conant K, Wang Y, Szklarczyk A, et al. Matrix metallopro- teinase-dependent shedding of intercellular adhesion molecule-5 occurs with long-term potentiation [J]. Neuro- science, 2010, 166(2): 508-521.
[6] 杨展能，姜靓婧，顾仕红，等. NMDA受体在匹罗卡品癫痫 小鼠海马星形胶质细胞活化中的作用[J]. 东南大学学报 （医学版），2017，36（2）：129-134.
[7] Carvajal FJ, Mattison HA, Cerpa W. Role of NMDA receptor-mediated glutamatergic signaling inchronic and acute neuropathologies [J]. Neural Plast, 2016, 6: 1-20.
[8] Yashiro K and Philpot BD. Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity [J]. Neuropharmacology, 2008, 55(7): 1081- 1094.
[9] Di Maio R, Mastroberardino PG, Hu X, et al. Pilocarpine alters NMDA receptor expression and function in hippo- campal neurons: NADPH oxidase and ERK1/2 mechanisms [J]. Neurobiol Dis, 2011, 42(3): 482-495.
[10] Kim, JY, Ko, AR, Hyun HW, et al. PDI regulates seizure activity via NMDA receptor redox in rats [J]. Sci Rep, 2017, 7: 42491.
[11] Brzdak P, Wlodarczyk J, Mozrzymas JW, et al. Matrix meta- lloprotease 3 activity supports hippocampal epsp-to-spike plasticity following patterned neuronal activity via the regulation of NMDAR function and calcium flux [J]. Mol Neurobiol, 2017, 54: 804-816.
[12] Daoudal G, Debanne D. Long-term plasticity of intrinsic excitability: learning rules and mechanisms [J]. Learn Mem, 2003, 10(6): 456-465.
[13] 邓　镇，罗淼珊，赵元淑，等. GluN2A抑制剂对癫痫持续 状态大鼠脑内P-糖蛋白表达的影响[J]. 华中科技大学学 报（医学版），2014，43（2）：168-172.

更新日期/Last Update: 2018-03-05