羟氯喹对Toll样受体-9介导的干扰素-α表达水平的影响  

Effect of hydroxychloroquine on IFN-α mRNA expression mediated by TLR-9

作　　者：张曦[1] 金欧[1] 黄红月[1] 侯成成[1] 古洁若[1] 

机构地区：[1]中山大学附属第三医院风湿免疫科,广州510630

出　　处：《新医学》2014年第6期378-381,共4页Journal of New Medicine

基　　金：中华医学会临床医学专项科研基金(12040700370)

摘　　要：目的初步探讨羟氯喹对Toll样受体-9(TLR-9)介导的人外周血单个核细胞(PBMC)中IFN-α表达水平的影响。方法提取健康志愿者的PBMC。分别将PBMC与0、0.375、0.75、1.5、3.0、6.0μg/ml TLR-9激动剂ODN 2216共同培养12 h,以及与1.5μg/ml ODN 2216共同培养0、6、12、24、48 h,从细胞水平模拟SLE高表达IFN-α。然后用1.5μg/ml ODN 2216与PBMC共同培养6 h,加入羟氯喹1.25μg/ml(实验组)及等量的培养基(阳性对照组),在未加入ODN 2216的PBMC内加入等量的培养基(空白对照组),继续培养12 h后用实时荧光定量PCR法检测并比较各组PBMC中IFN-αmRNA表达水平。结果 PBMC与1.5μg/ml ODN 2216共同培养6 h时,IFN-αmRNA表达水平最高(P<0.01)。阳性对照组PBMC中IFN-αmRNA表达水平明显高于空白对照组(P<0.01)。与阳性对照组相比,实验组PBMC中IFN-αmRNA表达水平明显降低(P<0.05)。结论羟氯喹可明显抑制经TLR-9介导的IFN-α高表达。Objectives To preliminarily investigate the effect of hydroxychloroquine on interferon-α（IFN-α）expression mediated by Toll like receptor-9 （TLR-9 ）in human peripheral blood mononuclear cells （PBMCs）. Methods PBMCs were freshly isolated from healthy donors. PBMCs were cultured with 0, 0.375,0.75,1.5,3.0,6.0 μg/ml TLR-9 agonist （ODN2216）for 12 h,or with 1.25 μg/ml ODN2216 for 0,6,12,24,48 h to mimic high expression of IFN-αin patients with SLE at the cell level. Then PBMCs were cultured with 1.5 μg/ml ODN 2216 for 6 h,and then treated with 1.25 μg/ml hydroxychloroquine （experiment group）or the same volume of medium （positive control group）,and cultured for 12 h. PBMCs without any treatment were used as control group. Afterward,the expressions of IFN-αamong three groups were detected by real-time quantitative PCR. Results When PBMCs were treated with 1.5 μg/ml ODN 2216 for 6 h, IFN-αmRNA expression reached the highest level （P〈0.01）. The expression of IFN-αmRNA in PBMC in positive control group was significantly higher than that of the control group（P〈0.01）. Compared with the positive control group,the mRNA expression of IFN-αin experiment group was significantly lower （P〈0.05）.Conclusions High expression of IFN-αmediated by TLR-9 may be inhibited by Hydroxychloroquine.

关 键 词：羟氯喹 干扰素-Α TOLL样受体-9 系统性红斑狼疮 

分 类 号：R593.2[医药卫生—内科学]