糖皮质激素对小胶质细胞内钙的影响  

Effects of glucocorticoids on intracellular calcium in microglial cells

作　　者：何舒翘 钱旭[1] 张贵平[1] 张维文[1] 张梅[1] 

机构地区：[1]广州医科大学药学院药理教研室,广州广东511436

出　　处：《中国药理学通报》2017年第6期878-883,共6页Chinese Pharmacological Bulletin

基　　金：广东省科技计划资助项目(No 2013B022000096);广东省自然科学基金资助项目(No 2016A030313568)

摘　　要：目的观察糖皮质激素对小胶质细胞内钙的影响并初步探讨其机制。方法体外培养神经小胶质细胞株BV-2,使用Fluo3-AM作为钙荧光染料,激光共聚焦显微镜实时扫描观察氢化可的松处理后BV-2细胞内钙浓度的动态变化情况。结果氢化可的松和阳性对照药尼古丁均能显著升高BV-2细胞内钙水平(P<0.05);实时扫描显示氢化可的松即刻引起细胞内钙升高,15 s左右达到峰值,持续约10 s后开始下降,200 s左右恢复至基态,并且这一作用显示出与尼古丁升高细胞内钙效应的一致性。糖皮质激素受体拮抗剂RU486不能取消氢化可的松升高BV-2细胞内钙的效应(P>0.05);而α7烟碱型乙酰胆碱受体(α7nAChR)阻断剂甲基牛扁亭碱(MLA)可以拮抗氢化可的松升高BV-2细胞内钙的效应(P<0.05)。结论氢化可的松通过影响α7nAChR升高小胶质细胞内钙水平,这一作用不但证实了糖皮质激素的非基因组效应,同时提示糖皮质激素可能作为α7nAChR的内源性配体。Aim To explore the effects of hydrocortisone on intracellular calcium in microglial cells. Methods The intracellular calcium was measured by instantaneous scanning with confocal laser microscope( CLM) in BV-2 cells,and fluo3-AM was used to dye the intracellular calcium. Results Both hydrocortisoneand nicotine could obviously increase intracellular calcium in BV-2 cells( P < 0. 05). It was indicated by instantaneous scanning with CLM that hydrocortisone induced the rising of intracellular calcium immediately,and reached the peak about at the fifteenth second,and sustained for 10 seconds,then declined to baseline at 200 th second. The effect of hydrocortisone on intracellular calcium exhibited a highly consistency with nicotine. Antagonist of glucocorticoid receptors RU486 could not abolish the rising of intracellular calcium induced by hydrocortisone( P > 0. 05); but the blockerof α7 nicotinic acetylcholine receptor( α7nAChR)methyllycaconitine could suppress the rising of intracellular calcium induced by hydrocortisone( P < 0. 05).Conclusion Hydrocortisone enhances intracellular calcium via α7nAChR in microglial cells,which not only demonstrates the non-genomic effect of glucocorticoid,but also suggests that glucocorticoid could serve as endogenous ligand of α7nAChR.

关 键 词：糖皮质激素 小胶质细胞 α7nAChR 尼古丁 甲基牛扁亭碱 

分 类 号：R322.8[医药卫生—人体解剖和组织胚胎学] R348.1[医药卫生—基础医学]