米诺环素对大鼠皮质神经元的毒性及N-甲基-D-天冬氨酸损伤的保护作用  

Neurotoxicity of minocycline and its protective effect on N-methyl-D-aspartate-induced damage in rat cortical neurons

作　　者：王一奇[1] 魏尔清[1] 

机构地区：[1]浙江大学医学院药理学教研室,浙江杭州310031

出　　处：《中国药理学与毒理学杂志》2004年第3期184-188,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助 ( 30 2 714 98)~~

摘　　要：目的　更全面地了解米诺环素对中枢神经系统的作用。方法　神经元与不同浓度米诺环素和(或 )N 甲基 D 天冬氨酸 (NMDA)作不同时间处理后 ,观察细胞形态 ,并以MTT试验评价细胞活性。结果　米诺环素 135 μmol·L- 1处理 2 4h明显降低体外培养 4 ,7,10d神经元的活性 (P <0 .0 1) ,13.5μmol·L- 1以下则无明显影响 ;4 5 ,135 μmol·L- 1米诺环素处理 3h对体外培养 10d神经元活性没有影响 ,处理 2 4h则活性明显下降 (P <0 .0 1)。米诺环素 4 5 ,135 μmol·L- 1可保护 5 0 μmol·L- 1NMDA损伤3h后的神经元活性 ,但对 15 μmol·L- 1NMDA损伤2 4h后无效 ;15 μmol·L- 1米诺环素则仅对 15 μmol·L- 1NMDA损伤 2 4h后有效。结论　米诺环素对大鼠原代皮质神经元有双重作用 ,高浓度长时间处理有毒性作用 ,但高浓度能保护神经元NMDA急性损伤 。AIM For comprehensive understanding the action of minocycline on central nervous system. METHODS Cortical neurons were isolated from new born rats, primarily cultured for different days, treated by minocycline and/or N methyl D aspartate(NMDA) at different concentrations for different durations. After treatment, neurons were photographed, and their viability was evaluated by MTT assay. RESULTSMinocycline cultured at 135 μmol·L-1 for 24 h markedly reduced the viability of the neurons at 4, 7, 10 d in vitro (P<0.01), but had no effect at 13.5 μmol·L-1 or less. Minocycline at 45 and 135 μmol·L-1 for 3 h did not reduce the viability of the neurons at 10 d in vitro, but reduced the viability when treated for 24 h. On the other hand, minocycline at 45 and 135 μmol·L-1 protected the neurons against the damage induced by 50 μmol·L-1 NMDA for 3 h, but had no effect on the damage induced by 15 μmol·L-1 NMDA for 24 h. However, a lower concentration of minocycline (15 μmol·L-1) could protect against the damage induced by 15 μmol·L-1 NMDA for 24 h. CONCLUSION Minocycline possesses both toxic and neuroprotective effects on rat primary cortical neurons. It can damage the neurons under longer exposure at higher concentrations, but protect the neurons from acute damage at higher concentrations and delay the damage at lower concentrations.

关 键 词：米诺环素 神经元 毒性 N-甲基-D-天冬氨酸 

分 类 号：R96[医药卫生—药理学]