双相障碍抑郁相患者T细胞免疫功能的研究

发布时间：2018-04-24 07:51

本文选题：双相障碍 + 细胞因子　；参考：《浙江大学》2017年硕士论文

【摘要】：目的:探讨双相障碍抑郁相与外周血T细胞免疫功能的相关性,检测患者外周血T淋巴细胞亚群和相关细胞因子IL-2、IL-4、IL-6、IL-10、TNF-α和IFN-γ的水平,以及T细胞和单核细胞表面共抑制分子TIM-3、PD-1及其配体PD-L1和PD-L2的表达。方法:采用流式细胞术测定23例双相障碍抑郁相患者(BD)及20例健康对照(HC)外周血T淋巴细胞亚群百分含量以及T细胞和单核细胞表面共抑制分子TIM-3、PD-1及其配体PD-L1和PD-L2的表达,并结合临床参数(发病年龄、总病程、发病次数、HDRS-17评分、MADRS评分和YMRS评分)做相关分析。采用CBA法检测 23 例 BD 患者及 20 例 HC 血清中 IL-2、IL-4、IL-6、IL-10、TNF-α 和 IFN-γ的水平。结果:双相障碍抑郁相组外周血细胞毒性T细胞(CD3+CD8+)的表达明显低于健康对照组(22.50±6.73 vs.29.45±6.80,P=0.002),有统计学差异;CD3+CD8+T细胞TIM-3+表达明显高于健康对照组(11.45±4.15vs.7.81±2.44,P= 0.011),有统计学差异;单核细胞表面PD-L2的表达明显低于健康对照组(24.90±10.84 vs.36.74±14.29,P=0.014),有统计学差异。相关性分析显示:CD3+CD8+T细胞的百分含量与发病年龄呈负相关(P=0.034和ρ=0.444);CD3+CD8+T细胞TIM-3+的表达与MADRS评分呈负相关(P=0.075和ρ= 0.457)。双相抑郁组血清IL-6表达水平明显高于健康对照组(10.47±1.98vs.0.44±0.68,P= 0.007),有统计学差异;血清中IL-2、IL-4、IL-10、TNF-α和IFN-γ的表达水平均低于检测下限,两组间比较未发现有统计学差异。结论:1、双相障碍抑郁相患者存在T淋巴细胞亚群的紊乱,CD3+CD8+T细胞的表达水平下降,因此检测T淋巴细胞亚群能更客观地反映双相障碍抑郁相患者的T细胞免疫功能。2、双相障碍抑郁相患者T细胞表面共抑制分子TIM-3、单核细胞表面PD-L2的表达水平出现了改变,提示共抑制分子可能参与了双相障碍的发病机制,并为未来从共抑制分子水平治疗双相障碍提供理论基础。3、血清IL-6的水平在BD组明显增高,证实细胞因子的异常参与了双相障碍抑郁相的发病机制存在关联性。4、本研究进一步支持了双相障碍患者存在免疫功能的失调,在未来的研究中,需要更多关注免疫抑制性分子在精神疾病中的作用。
[Abstract]:Objective: to investigate the correlation between bipolar disorder depression phase and T cell immune function in peripheral blood, and to detect the levels of TNF- 伪 and IFN- 纬 in peripheral blood T lymphocyte subsets and related cytokines IL-2, IL-4, IL-6, IL-10, TNF- 伪 and IFN- 纬 in patients with bipolar disorder. In addition, the expression of TIM-3 / PD-1 and its ligands, PD-L1 and PD-L2, on the surface of T cells and monocytes were also inhibited. Methods: flow cytometry was used to determine the percentage of T lymphocyte subsets in peripheral blood of 23 patients with bipolar disorder and 20 healthy controls, and the expression of TIM-3mPD-1 and its ligand PD-L1 and PD-L2 on the surface of T cells and monocytes. Correlation analysis was made with clinical parameters (age of onset, total course of disease, frequency of onset, HDRS-17 score, MADRS score and YMRS score). The levels of IL-2TNF- 伪 and IFN- 纬 in serum of 23 patients with BD and 20 patients with HC were detected by CBA method. Results: the expression of CD3 CD8 in peripheral blood cytotoxic T cells in bipolar disorder depression group was significantly lower than that in healthy control group (22.50 卤6.73 vs.29.45 卤6.80 vs.29.45 卤6.80 P0. 002), and the expression of CD3 CD8 T cell TIM-3 was significantly higher than that in healthy control group (11.45 卤4.15vs.7.81 卤2.44 P = 0.011). The expression of PD-L2 on monocyte surface was significantly lower than that in healthy control group (24.90 卤10.84 vs.36.74 卤14.29 vs.36.74 卤14.29 vs.36.74 卤0.014 4). Correlation analysis showed that there was a negative correlation between the percentage of CD3 CD8 T cells and the age of onset. The expression of TIM-3 on CD3 CD8 T cells was negatively correlated with the MADRS score (P 0. 075 and 蟻 = 0. 457). The level of serum IL-6 expression in bipolar depression group was significantly higher than that in healthy control group (10.47 卤0.68 卤0.68 P = 0.007, P = 0.007, P = 0.007), and the levels of IL-2-, IL-4, IL-10, TNF- 伪 and IFN- 纬 in serum were lower than those in control group, and there was no significant difference between the two groups. Conclusion the expression level of CD3 CD8 T cells in the patients with bipolar disorder and depression is decreased in the presence of T lymphocyte subsets. Therefore, the detection of T lymphocyte subsets can more objectively reflect the T cell immune function of the patients with bipolar disorder and depression, the expression of TIM-3 on the surface of T cells and the expression of PD-L2 on the surface of monocytes in patients with bipolar depression. These results suggest that the co-suppressor molecules may be involved in the pathogenesis of bipolar disorder, and provide a theoretical basis for the treatment of bipolar disorders at the molecular level of co-suppression. The serum IL-6 level in BD group was significantly higher than that in BD group. It is confirmed that the abnormal cytokines are involved in the pathogenesis of bipolar disorder depression phase. 4. This study further supports the existence of disorder of immune function in patients with bipolar disorder. More attention needs to be paid to the role of immunosuppressive molecules in mental disorders.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.4

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