褪黑素对低氧诱导的BV-2小胶质细胞CD45表达增高的抑制作用(英文) 被引量：2

Inhibitory effect of melatonin on the elevation of CD45 expression induced by hypoxia in BV-2 microglia

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摘要目的　研究褪黑素对低氧激活的小胶质细胞CD4 5表达的影响 ,以探讨褪黑素的抗衰老和抗阿尔茨海默病的作用机制。方法　体外培养BV 2小胶质细胞 ,用终浓度为 2 .0mmol·L- 1的连二亚硫酸钠作用 4 8h ,造成慢性低氧模型 ,药物处理组在低氧的同时给予褪黑素。相差显微镜下观察小胶细质胞形态学变化 ,流式细胞术测定缺氧状态下BV 2小胶质细胞表面CD4 5的表达 ;体外培养BV 2小胶质细胞用终浓度为 0 .0 1,0 .1,1.0 μmol·L- 1的褪黑素作用5min ,加入 2 0mg·L- 1的脂多糖 37℃孵育 12h ,Griess试剂法检测培养上清中NO的含量。结果　连二亚硫酸钠引起的低氧可明显增加BV 2小胶质细胞CD4 5的表达 ,荧光强度增至 2 3.9± 14 .2 (对照组为0 .80± 0 .73) ,低氧也可使小胶质细胞的形态发生阿米巴样变 ,而 0 .0 1,0 .1,1.0 μmol·L- 1的褪黑素可剂量依赖性地减少低氧诱导的CD4 5表达 ,抑制由低氧引起的小胶质细胞的阿米巴样变。但褪黑素对脂多糖诱导的BV 2小胶质细胞培养液中NO的升高无明显抑制作用。结论　褪黑素抑制小胶质细胞的激活与其抗氧化作用密切相关。 AIM To study the action of melatonin on the expression of CD45 in BV 2 microglia and the influence of melatonin on BV 2 microglia activation so as to explore the antiaging and anti Alzheimer′s disease mechanisms of melatonin. METHODS Hypoxia in cultured BV 2 microglia was induced by sodium dithionite 2.0 mmol·L -1 for 48 h. The expression of CD45 on the BV 2 microglia surface was measured by flow cytometry, the morphological changes of BV 2 microglia were photographed with the phase contrast microscope. BV 2 microglia were exposed to 20 mg·L -1 lipopolysaccharides 5 min after treated with 0.01, 0.1, 1.0 μmol·L -1 of melatonin, then incubated for 12 h. NO level in the medium was determined by Griess reagent. RESULTS The fluorescent intensity produced by CD45 expression in BV 2 microglia increased from 0.80±0.73 (normal control) to 23.9±14.2 (hypoxia model). Melatonin (0.01, 0.1, 1.0 μmol·L -1 ) significantly inhibited the elevation of CD45 expression in microglia in a concentration dependent manner, the fluorescent intensity is 9.3±3.1, 7.0±4.85 and 5.4±1.0, respectively. Melatonin could inhibit the morphological change of BV 2 microglia to amebocyte. But melatonin did not antagonize the increase in NO level in the medium induced by lipopolysaccharide. CONCLUSION Melatonin inhibiting the microglia activation by its anti oxidative action might be an important theoretical basis of anti inflammation and anti Alzheimer′s disease effects.

作者姚景春张庆柱张世玲程艳娜纪建波

机构地区山东大学药学院药理学教研室

出处《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2004年第4期259-263,共5页 Chinese Journal of Pharmacology and Toxicology

关键词褪黑素低氧诱导作用 BV-2小胶质细胞 CD45表达抑制作用抗原 melatonin microglia antigen, CD45 hypoxia

分类号 R96 [医药卫生—药理学]

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