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| 大鼠短暂性脑缺血后去氢表雄酮的神经保护作用和神经毒性 |
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| DHEA-neuroprotection and -neurotoxicity after transient cerebral ischemia in rats |
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| Li Z., Cui S., Zhang Z., Zhou R., Ge Y., Sokabe M., Chen L. 2009/5/29 18:38:57 |
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Journal of Cerebral Blood Flow and Metabolism, 2009, Volume 29, Issue 2
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| Dehydroepiandrosterone (DHEA) has been implicated not only to prevent N-methyl-D-aspartate (NMDA)-induced neurotoxicity but also to enhance Ca 2+ influx through NMDA receptor (NMDAr). However, these DHEA effects, which would produce inconsistent outcomes about neuronal damages, are not well studied in ischemia-induced cerebral damages. Herein, we report that a single administration of DHEA (20 mg/kg) during 3 to 48 h after transient global cerebral ischemia in rats exerted neuroprotective effects such as reduction of ischemia-induced neuronal death in the hippocampal CA1 and improvement of ischemia-induced deficits in spatial learning. By contrast, at 1 h before or after ischemia, the administration of DHEA exacerbated the ischemia-induced neuronal death and learning impairment. This DHEA neurotoxicity appeared to be caused by DHEA itself, but not through its metabolite testosterone, and was inhibited by a pretreatment with the NMDAr blocker MK801 or the sigma-1 (σ1) receptor antagonist NE100. However, the DHEA neuroprotection was blocked by NE100. These results show that DHEA not only provides robust ischemic neuroprotection with a long therapeutic opportunity but also exerts neurotoxicity when administered during ischemia and early reperfusion, which points to the importance of administration timing of DHEA in the clinical treatment of brain damages by the transient brain ischemia including stroke. © 2009 ISCBFM All rights reserved. |
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| Correspondence Address: Sokabe, M.; Department of Physiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan; email: msokabe@med.nagoya-u.ac.jp |
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 疾病资源中心
王燕燕 王曙
上海交通大学附属瑞金医院内分泌科
患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。
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