选择性5-羟色胺再摄取抑制剂对小胶质细胞不同活化途径的影响  

The effect of fluoxetine and escitalopram on the activation of microglia

作　　者：苏凡[1] 易宏伟[2] 张志珺[2] 

机构地区：[1]东南大学医学院 [2]东南大学附属中大医院神经内科,南京210009

出　　处：《中华精神科杂志》2014年第6期364-370,共7页Chinese Journal of Psychiatry

摘　　要：目的 探讨SSRIs氟西汀和艾司西酞普兰对于小胶质细胞不同活化途径的影响.方法 新生2 dSD大鼠脑组织经洗涤、分离、消化、过筛网、离心等处理,获得原代小胶质细胞.将BV2细胞系组和原代细胞组进一步分亚组如下：空白对照组、M1型模型组、M2型模型组、氟西汀组和艾司西酞普兰组,干预24h后使用实时定量聚合酶链式反应（real-time quantitative polymerase chain reaction,RT-PCR）、酶联免疫吸附测定（enzyme linked immunosorbent assay,ELISA）和免疫印迹法测定相关炎症指标表达水平.结果 （1）M1型活化：RT-PCR示氟西汀可显著降低脂多糖联合干扰素-γ（LPS＋INF-γ）诱导的BV2细胞白细胞介素1β（interleukin 1β,IL-1β）、IL-6、肿瘤坏死因子a（tumor necrosis factor,TNF-a）和诱导型一氧化氮合成酶（inducible nitric oxide synthase,iNOS）mRNA表达（均P＜0.05）.氟西汀和艾司西酞普兰均可显著抑制LPS＋ INF-γ诱导的原代小胶质细胞IL-6（均P＜0.01）、TNF-a（P =0.018、0.029）和iNOS（均P=0.005）mRNA表达.免疫印迹法示氟西汀和艾司西酞普兰可显著抑制LPS＋ INF-γ诱导的BV2细胞Iba-1 （P ＜0.01、P=0.002）、CD86（均P＜0.01）蛋白表达.氟西汀和艾司西酞普兰均可显著抑制LPS＋ INF-γ诱导的原代小胶质细胞CD86表达（均P＜0.01）.ELISA示氟西汀可显著抑制LPS＋ INF-γ诱导的BV2细胞TNF-a（P=0.003）和IL-1 β（P=0.002）分泌.氟西汀和艾司西酞普兰可显著抑制LPS＋ INF-γ诱导的原代小胶质细胞IL-1β分泌（均P＜0.01）.原代小胶质细胞各组间TNF-a分泌差异无统计学意义（F=4.627,P=0.053）,进一步组间比较示与模型组[（11.6±1.1）g/L]相比,艾司西酞普兰组[（20.2±1.9） g/L]TNF-a表达增高（P=0.012）.（2）M2型活化：RT-PCR示氟西汀可显著提高IL-4诱导的原代小胶质细胞IL-10 mRNA表达（P=0.036）.免疫印迹法示氟西汀可显著提高IL-4诱导的BV2细胞（P=0.016）�Objective To explore the effect of the selective serotonin reuptake inhibitors （SSRIs）：fluoxetine and escitalopram on the activation of microglia.Methods The experiment involved two groups of cells,the cell line （BV2） and primary microglia cell,and each group was divided into five sub-groups,the control group,M1 model group,M2 model group,the fluoxetine group and the escitalopram group.After intervention for 24 hours the inflammation index were measured by RT-PCR,enzyme linked immunosorbent assay（ELISA） and Western blot.Results （1） M1 activation：Detected by RT-PCR,fluoxetine significantly reduced the LPS ＋ INF-γinduced expressions of IL-1 β （P =0.001）,IL-6 （P 〈 0.01）,tumor necrosis factor （TNF-a） （P =0.016） and inducible nitric oxide synthase （iNOS） （P =0.005） mRNA for BV2.Both fluoxetine and escitalopram significantly reduced the LPS ＋ INF-γ induced expressions of IL-6 （P 〈0.01 respectively）,TNF-a （P =0.018,0.029 respectively） and iNOS （P =0.005 respectively） mRNA for primary cells.Detected by Western blot,both fluoxetine and escitalopram significantly reduced LPS ＋ INF-γ induced expressions of Iba-1 （P 〈 0.01,P =0.002 respectively） and CD86 （P 〈 0.01 respectively） for BV2 cells.For primary microglia cells,both fluoxetine and escitalopram significantly reduced LPS ＋ INF-γinduced expressions of CD86 （P 〈0.01 respectively）.Detected by ELISA,fluoxetine significantly reduced the LPS ＋ INF-γ induced releases of TNF-a （P =0.003） and IL-1β （P =0.002） for BV2 cells.For primary microglia cells,both fluoxetine and escitalopram significantly reduced the LPS ＋ INF-γ induced releases of IL-1 β （P 〈 0.01 respectively）.The TNF-a releases of escitalopram group （（20.2 ± 1.9） g/L were significantly higher than the model group （11.6 ± 1.1） g/L,P =0.012）.（2）M2 activation：Detected by RT-PCR,fluoxetine significantly improved the IL-4 induced IL-10mRNA expressions for primary cells （P =0.036）.Detecte

关 键 词：抑郁症 小胶质细胞 经典型活化 替代型活化 选择性5-羟色胺再摄取抑制剂 

分 类 号：R749.4[医药卫生—神经病学与精神病学]