摘要
目的观察脱氢表雄酮对大鼠大脑皮质神经元谷氨酸释放的影响。方法原代培养的SD大鼠大脑皮质神经元经不同浓度(1×10-7、1×10-6、1×10-5mol·L-1)和不同作用时间(0.5,1,1.5,2,5,24,36,48,72h)的脱氢表雄酮处理后,采用OPA-巯基乙醇柱前衍生,荧光检测-高效液相色谱法测定细胞培养液中谷氨酸的含量。结果与对照组相比,不同浓度的脱氢表雄酮处理后,细胞培养液中谷氨酸的水平均下降(P<0.05或P<0.01);与对照组相比,脱氢表雄酮处理组1,1.5,2,5,24,36,48,72h细胞培养液中谷氨酸的水平均下降(P<0.05或P<0.01)。结论脱氢表雄酮可抑制神经元谷氨酸的释放,这可能介导了其对抗谷氨酸兴奋性毒性的作用。
Abstract
OBJECTIVE To investigate the effect of dehydroepiandrosterone on the levels of glutamate released from primary cultured rat cerebral cortical neurons. METHODS Primary cultured rat cerebral cortical neurons were treated with different concentrations(1×10-7,1×10-6,1×10-5mol·L-1) of dehydroepiandrosterone and the concentrations of glutamate in cell culture media at different times (0.5,1,1.5,2,5,24,36,48,72 h after treatment) were measured by OPA-mercaptoethanol precolumn derivatization technique and HPLC-FLD. RESULTS Compared with control group , different concentrations of dehydroepiandrosterone treatment significantly reduced the levels of glutamate(P<0.05 or P<0.01). Compared with control group,dehydroepiandrosterone treatment significantly reduced the levels of glutamate at 1,1.5,2,5,24,36,48,72 h(P<0.05 or P<0.01). CONCLUSION Dehydroepiandrosterone could inhibit the release of glutamate,which may mediate its role against excitotoxicity caused by glutamate.
关键词
脱氢表雄酮 /
谷氨酸 /
大脑皮质
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Key words
dehydroepiandrosterone /
glutamate /
cerebral cortex /
neuron
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薛改;吴红海;侯艳宁.
脱氢表雄酮对原代培养大鼠大脑皮质神经元谷氨酸释放的影响[J]. 中国药学杂志, 2009, 44(04): 262-265
XUE Gi;WU Hong-hi;HOU Yn-ning.
Effects of Dehydroepiandrosterone on Glutamate Released from Primary Cultured Rat Cerebral Cortical Neurons [J]. Chinese Pharmaceutical Journal, 2009, 44(04): 262-265
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参考文献
[1] KAWATO S,YAMADA M,KIMOTO T. Brain neurosteroids are 4th generation neuromessengers in the brain:Cell biophysical analysis of steroi signal transduction[J]. Adv Biophy,2003,37:1-48.
[2] YOUNG A H,GALLAGHER P,PORTER R J. Elevation of the cortisoldehydroepiandrosterone ratio in drug-free depressed patients [J]. Am J Psychiatry,2002,159(7):1237-1239.
[3] WEILL-ENGERER S,DAVID J P,SAZDOVITCH V,et al. Neurosteroid quantification in human brain regions:comparision between Alzheimer's and nondemented patients [J].J Clin Endocrinol Metab,2002,87(1):5138-5143.
[4] XIE L,SUN H Y,GAO J,et al. Functions and mechanisms of dehydroepiandrosterone in nervous system[J]. Progr Physiol Sci(生理科学进展),2006,37(4):335-338.
[5] KURATA K,TAKEBAYASHI M,MORINOBU S,et al. Beta-estradiol dehydroepiandrosterone and dehydroepiandrosterone sulfate protect against n-methyl-d-aspartate-induced neurotoxicity in rat hippocampsl neurons by different mechanisms[J]. Pharmacol Exp Ther,2004,311(1):237-245.
[6] WU H H,WANG N,HOU Y N. Changes of neurosteroids levels in nucleus accumbens and plasma of rat morphine conditioned place preference after a footshock iuduced reinstatement[J]. Chin Pharm J(中国药学杂志),2006,41(13):986-989.
[7] XUE G,WU H H,HOU Y N. Effects of progesterone on amino acid neurotransmitters released from rat cerebral cortical neurons[J]. Chin Pharmacol Bull(中国药理学通报),2008,24(5):680-683.
[8] JING P,HOU Y N. Effcets of morphine on neurosteroidogenesis of primary cultured rat cerebral cortical neurons[J]. Chin Pharmacol Bull(中国药理学通报),2006,22(12):1489-1493.
[9] MEI H S. Protective effects of dipfluzine on focal cerebral ischemia-reperfusion injury in rats[D].Shijiazhang:Hebei Medical University,2004.
[10] LHULLIER F L R, RIERA N G,NICOLAIDIS R,et al. Effect of dhea glutamate release from synaptosomes of rats at different ages[J]. Neurochem Res,2004,29(2):335-339.
[11] KUMAR A,ZOU L,YUAN X,et al. N-methyl-D-aspartate receptors:Transient loss of nr1/nr2a/nr2b subunits after traumatic brain injury in a rodentmodel[J]. Neurosci Res,2002,67(6):781-786.
[12] YANG N,LIU Y Y,ZUO P P. Dehydroepiandrosterone and 7-oxo- dehydroepiandrosterone(7-oxo-DHEA) protected hippocampal neurons against neurotoxicity induced by glutamate[J]. Chin Pharmacol Bull(中国药理学通报),2004,20(7):750-753.
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脚注
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基金
河北省自然科学基金资助项目(C2005000834)
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