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P0.05);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(P0.01);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P0.05)。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。

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 significa

目的：研究ATP敏感的钾离子通道开放剂二氮嗪（diazoxide）预处理对Aβ1～42作用原代培养神经元N－甲基－D－天冬氨酸（NMDA）受体2B（NR2B）亚基蛋白表达的影响。方法原代培养大鼠皮层海马神经元并进行鉴定，将细胞随机分为对照组、单纯Aβ1～42干预组、二氮嗪预处理1h后Aβ1～42干预组（Aβ1～42＋diazoxide）、单纯二氮嗪预处理组，并采用免疫印迹检测不同时间点（24 h、72 h）细胞 NR2B亚基蛋白表达水平的变化。结果 Aβ1～42（2μmol／L）作用神经元24 h 后，与对照组相比，单纯 Aβ1～42干预组和 Aβ1～42＋diazoxide 组的 NR2B 亚基蛋白表达均无明显改变。Aβ1～42作用神经元72 h后，与对照组比较，单纯Aβ1～42组NR2B亚基蛋白表达量显著升高（P＜0．05）；而与单纯Aβ1～42干预组相比，Aβ1～42＋diazoxide组NR2B亚基蛋白表达明显降低（P＜0．05）。结论 Aβ1～42作用原代培养神经元72 h，能够显著增加神经细胞NR2B亚基蛋白的表达量；同时，二氮嗪能拮抗Aβ1～42所引起的NR2B亚基蛋白表达量升高，提示二氮嗪可能通过NMDA受体通路影响Aβ1～42的细胞毒性作用。

Objective To study the effects of pretreatment of ATP sensitive potassium channel opener diazoxide on neural NR2B subunit protein expression induced by Aβ1~42 .Methods The primary neurons were cultured and evaluated, then neurons were randomly di-vided into control group, Aβ1~42 treatment group, diazoxide pretreatment for 1 h +Aβ1~42 group( Aβ1~42+diazoxide) and simple diazoxide group, the protein expression level of NR2B subunit was determined by Western blotting for different times(24 h and 72 h).Results Being exposed to Aβ1~42 for 24 h, compared with the control group, the protein expression level of NR2B subunit of both Aβ1~42 group and Aβ1~42+diazoxide group have no significant difference.However, compared with control group, the protein expression level of NR2B subunit of Aβ1~42 group significantly increases for 72 h( P<0.05); Compared with Aβ1~42 group, the protein expression level of NR2B subunit of Aβ1~42+diazoxide group significantly decreases(P<0.05).Conc

糖尿病认知功能障碍(CID)是糖尿病的严重慢性并发症之一,其发病机制目前尚未完全清楚。近年来,人们发现N-甲基-D-天冬氨酸受体(NMDAR)及其亚基NR2A、NR2B不仅参与中枢神经系统的发育和学习记忆的形成,且其分布及表达与CID的发生、发展密切相关。

Cognitive impairment in diabetes (CID) is a severe chronic complication of diabetes mellitus, and its pathogenesis has not yet been fully understood. Increasing evidence has shown that the distribution and expression of N-methyl-D-aspartame receptor (NMDAR) and subunits NR2A and NR2B, which all participated in the development of the central nervous system and formation of learning and memory, are correlated with the occurrence and development of CID.

目的研究表明硫化氢(H2S)能调节大脑N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptors,NMDARs)的功能,但其在脑复苏中的作用仍需进一步阐明。文中通过观察H2S复合浅低温对大鼠全脑缺血再灌注后海马NMDARs的亚单位NR2A、NR2B及其环磷酸腺苷反应元件结合蛋白(phospho-cAMP response element binding protein,p-CREB)信号通路的影响,旨在探讨H2S是否存在脑复苏作用及其发挥作用的潜在机制。方法雄性SD大鼠随机分为5组(n=20):假手术组、模型组、浅低温组、硫氢化钠(NaHS)组、浅低温+NaHS组。采用Pulsinelli-Brierley四血管阻塞法建立大鼠全脑缺血再灌注损伤模型,缺血15min再灌注即刻NaHS组和浅低温+NaHS组腹腔注射14μmol/kg NaHS,浅低温组和浅低温+NaHS组行体表降温至肛温32~33℃。6h后断头取海马,分别采用分光光度计法测H2S的含量,Western blot法测NR2A、NR2B以及p-CREB的表达,RT-PCR法测脑源性神经营养因子(brain derived neurotrophic factor,BDNF)mRNA的水平,每组分别取4只于再灌注72 h取脑组织行HE染色观察CA1区锥体细胞病理改变。结果 1与假手术组海马组织H2S含量(15.2±2.0)nmol/g相比,各组均升高(P0.05);与模型组的H2S含量(25.2±3.5)nmol/g相比,浅低温组(26.5±3.5)nmol/g略升高(P0.05),而NaHS组(37.5±4.0)nmol/g和浅低温+NaHS组(38.7±4.4)nmol/g显著升高(P0.05);2与假手术组相比,各组NR2A、NR2B的灰度值均增高(P0.05),且模型组和浅低温组NR2A/NR2B1,NaHS组和浅低温+NaHS组NR2A/NR2B1;3与模型组的p-CREB表达(0.55±0.06)相比,浅低温组(0.99±0.15)、NaHS组(1.05±0.12)、浅低温+NaHS组(1.02±0.15)显著升高(P0.05);与模型组的BDNF mRNA表达量(0.83±0.12)相比,浅低温组(1.11±0.13)、NaHS组(1.27±0.16)、浅低温+NaH

Objective Research has indicated that hydrogen sulfide(H2S) can regulate the function of N-methyl-D-aspartate re-ceptors(NMDARs) in the brain, but its effect on brain resuscitation requires further investigation.The study was to speculate the effect of H2 S on brain resuscitation as well as the underlying mechanism of neuroresuscitation by investigating the effects of hydrogen sulfide and hypo-thermia on the expression of NR2A, NR2B and phospho-cAMP response element binding protein (p-CREB) of NMDARs in the hippocampus after global cerebral ischemia following by reperfusion. Methods 100 male SD rats were randomly divided into five groups(n=20):sham operation group, model group, mild hypothermia group, NaHS group, NaHS combined mild hypothermia group.Pulsinelli-Brierley four-ves-sel occlusion method was induced to build the injury rat model by reperfusion after global cerebral ischemia .After 15 minutes''ischemia, im-mediate injection of 14μmol/kg NaHS was performed intraperi

本文旨在探讨慢性应激性抑郁发生过程中眶额叶多巴胺D1受体对谷氨酸(glutamic acid,Glu)及其N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体的NR2B亚基的影响。实验通过建立慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)抑郁模型,结合眶额叶微量注射多巴胺D1受体激动剂SKF38393和多巴胺D1受体拮抗剂SCH23390,运用糖水偏爱测试、悬尾实验和敞箱实验等方法检测动物的行为表现,采用高效液相色谱法(high-performance liquid chromatography,HPLC)和蛋白质免疫印迹法(Western blot,WB)来检测眶额叶内谷氨酸、多巴胺含量及NR2B和多巴胺D1受体的表达。结果显示,与对照组相比,CUMS组大鼠表现出明显的抑郁样行为变化,且眶额叶多巴胺含量降低,其D1型受体表达降低,谷氨酸含量升高,其NMDA受体的NR2B亚基也明显上调;注射SKF38393后可明显改善应激引起的抑郁样行为,且眶额叶谷氨酸含量显著下降,NMDA受体的NR2B亚基表达也有所降低;正常大鼠注射多巴胺D1受体拮抗剂SCH23390,大鼠表现出和CUMS模型组相似的抑郁样行为,且眶额叶谷氨酸含量升高,其NMDA受体的NR2B亚基也明显上调。以上结果表明,慢性不可预见性应激可能使眶额叶多巴胺释放减少,从而使谷氨酸过量释放,NMDA受体过度激活,导致抑郁发生。多巴胺抗抑郁作用是通过D1型受体抑制谷氨酸及其NMDA受体NR2B亚基表达来实现。

Stressors play a pivotal role in the occurrence of depressive illnesses. Disorders of monoamine neurotransmitters and their receptors may be the fundamental causes of depression. Additionally, abnormal expression of glutamic acid (Glu) and its receptor may be a major reason for depression. Consequently, the study of the relationship between monoamine and glutamic acid neurotransmitter in stress-induced depression has significances to reveal the profound mechanism of depression. NR2B subunits which are highly expressed in the cortex, hippocampus and olfactory bulb, are one of the key subunits of NMDA receptors. Orbital frontal cortex (orbital frontal cortex, OFC), which plays a significant role in higher brain function, such as emotional and complex behavior, is one of the major sub-regions of prefrontal. This study was to investigate the effect of orbital frontal cortex D1 dopamine receptor on Glu and its receptors, especially on NR2B subunits of N-methyl-D-aspartic acid (NMDA) recepto