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褪黑激素对大脑皮层谷氨酸释放及其神经毒性的拮抗作用(英文)

Antagonistic effects of melatonin on glutamate release and neurotoxicity in cerebral cortex

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【作者】 张庆柱贡岳松张均田

【Author】 ZHANG Qing-Zhu, GONG Yue-Song, ZHANG Jun-Tian(The Second Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciencesand Peking Union Medical College, Beijing 100050, China )

【机构】 中国医学科学院中国协和医科大学药物研究所药理二室中国医学科学院中国协和医科大学药物研究所药理二室 北京 中国 100050北京 中国 100050北京 中国 100050

【摘要】 目的:观察褪黑激素(Mel)对老年小鼠大脑皮层突触体谷氨酸(Glu)释放以及KCl,Glu在原代培养胎鼠脑细胞诱发的神经毒性的影响,以探讨Mel抗衰老的作用机制。方法:制备老年小鼠大脑皮层突触体,用RF-5000型双波长荧光分光光度计检测谷氨酸释放量。应用原代培养的大鼠皮层细胞MTT染色和乳酸脱氢酶(LDH)测定法评估神经元活性。结果:Mel能够抑制高浓度氯化钾(30mmol·L-1)诱发的老年小鼠大脑皮层突触体钙依赖性及非依赖性谷氨酸释放,抵抗KCl和Glu诱发的皮层细胞损伤,对神经元有保护作用。结论:Mel对大脑皮层突触体谷氨酸释放的抑制作用以及对大脑皮层神经元的保护作用可能是其抗衰老作用机制之一。

【Abstract】 AIM: To observe the effects of melatonin (Mel) on glutamate (Glu) release from the cortical synaptosomes in old mice and on neurotoxicity induced by KCl, Glu in cultured cortical cells of fetal rat and to explore the antiaging mechanism of Mel. METHODS: Glu release by the synaptosomes in old mouse cerebral cortex was detected in a spectrofluorophotometer. The neuronal viability in primary cultures from rat cerebral cortex was assessed using MTT stain and lactate dehydrogenase (LDH) efflux in the bathing medium. RESULTS: Mel inhibited the K+ (30 mmol·L-1)-induced Glu release from synaptosomes either in calcium dependent or independent conditions [ control (10.6±1.1), (9.2±0.7) μmol·g-1(protein); Mel 0.1 μmol·L-1(6.5±0.9), (7.5±0.6) μmol·g-1 (protein), respectively, P<0.01 vs control group), increased MTT activity (control 0.67 ±0.04, 0.81±0.03; Mel 0.1 μmol·L-1 0.715 ±0.023, 0.925±0.027, P < 0.01 vs control group] and decreased LDH efflux (control 0.400±0.016, 0.379±0.016; Mel 0.1 μmol· L-1 0.345± 0.021, 0.340±0.012, respectively, P<0.01 vs control group), therefore, protected the neuronal viability against KCl and Glu-induced injury. CONCLUSION: The inhibitory effect of Mel on Glu release from cortical synaptosome and the protective effect of Mel on cortical neurons against neurotoxicity are its antiaging mechanisms.

  • 【文献出处】 Acta Pharmacologica Sinica ,中国药理学报(英文版) , 编辑部邮箱 ,1999年09期
  • 【分类号】R96
  • 【被引频次】2
  • 【下载频次】8
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