抑郁症中糖皮质激素受体与CD4^+ CD25^+调节性T细胞的关系及其所致免疫失衡机制的初步探讨  

Preliminary study on the relationship between glucocorticoid receptor and CD4^+ CD25^+ Treg in immune disequilibrium of depression

作　　者：邱文静[1] 杨欢[1] 肖波[1] 杨乐[1] 李艺[1] 田晓琳[1] 胡波[1] 吴志国[1] 余庆皋[2] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410008 [2]湖南湘潭职业技术学院

出　　处：《中国神经精神疾病杂志》2009年第6期350-354,共5页Chinese Journal of Nervous and Mental Diseases

基　　金：湖南省教育厅资助科研项目(编号:07D080)

摘　　要：目的研究抑郁症患者外周血细胞因子白介素-10(IL-10)、转化生长因子β(TGF-β)的变化、CD4+ CD25+调节性T细胞(Treg)的数量及其特征性标志叉头样转录因子P3(Foxp3)的表达与糖皮质激素受体(GR)的表达之间的关系,探讨抑郁症患者免疫失衡的可能机制。方法纳入36例抑郁症患者和36名正常对照,根据Hamilton抑郁量表总分将患者划分为轻、中和重不同抑郁程度组;利用ELISA方法测定受试者外周血血清细胞因子IL-10、TGF-β浓度;逆转录-聚合酶链反应(RT-PCR)检测GR的α及β两种亚型(GRα、GRβ)、Foxp3 mRNA表达水平;免疫磁珠分离CD4+ CD25+ Treg,共聚焦显微镜观察Foxp3与GR在CD4+ CD25+ Treg上的共表达。结果与正常对照组比较,患者组血清IL-10、TGF-β的水平降低(P<0.05),外周血CD4+CD25+Treg数量及在CD4+T细胞中的比例明显少于对照组(P<0.01),且重度抑郁组上述指标明显低于中度和轻度抑郁组(P<0.01)。抑郁各组单个核细胞GRαmRNA和FoxP3 mRNA表达水平随抑郁程度而降低(P<0.01),GRβmRNA却在重度抑郁组表达增加。共聚焦显微镜下可观察到重度抑郁患者CD4+ CD25+ Treg上GR与Foxp3表达显著减少。结论糖皮质激素受体可能通过影响调节性T细胞的功能和数量在抑郁症患者免疫失衡的病理生理机制中发挥着重要的作用。Objective To study whether glucocorticoid receptor has any role in immune disequilibrium of major depression by examining serum levels of cytokine IL-10 and TGF-β and exploring the relationship between the expression of glucocorticoid receptor（GR） and the quantity of CD4 ＋ CD25＋ Treg. Methods The patients were selected based on CC- MD-3, and were categorized accroding to Hamilton depression rating scale. The concentrations of IL-10, TGF-β were detected using ELISA. The expressions of GRα,GRβ ,Foxp 3mRNA were detected by RT-PCR and β-actin was served as internal control. After CIM ＋ CD25 ＋ Treg were isolated by magnetic beads, the coxpression of the GR and Foxp3 in CD4＋ CD25＋ Treg was examined by confocal microscopy. Results Compared with the controls, the depressive patients, especially the severe depressive patients hadsignificant decreases in serum levels of IL-10 ,TGF-β （ P 〈 0. 05 ） expressions of GRαmRNA, Foxp3mRNA in CD4＋ CD25＋ Treg and proportion of CD4＋ CD25＋ Treg （ P 〈 0. 01 ）. In addition, severe depression had a significant increase in the expression of GRβmRNA. Furthermore, the co-expression of GR and Foxp3 was significantly decreased in CD4＋ CD25＋Treg in severe depressive patients. Conclusions The present results suggest that the glucocorticoid receptor plays a role in the immune imbalance of depression, probably through the regulation of T cell pathway.

关 键 词：调节性T细胞 抑郁症 糖皮质激素受体 叉头样转录因子P3 

分 类 号：R749.4[医药卫生—神经病学与精神病学]