IL-27、TNF-α和5-HT在CIA共病抑郁症大鼠模型中的表达特点

doi:10.3877/cma.j.issn.1674-0785.2019.04.009

目的

探讨肿瘤坏死因子-α（TNF-α）、白介素-27（IL-27）和5-羟色胺（5-HT）在胶原诱导的关节炎（CIA）共病抑郁症大鼠模型中的表达特点。

方法

通过复合造模思路，在Ⅱ型CIA大鼠模型基础上联合慢性不可预知温和刺激抑郁症模型，建立类风湿关节炎（RA）共病抑郁症大鼠模型。32只雌性Wistar大鼠随机分为4组：（1）正常对照组：每笼4只，正常饲养；（2）RA组：每笼4只，建模后正常饲养；（3）抑郁症组：每笼1只，与RA共病抑郁症组同时给予慢性不可预知温和刺激方法；（4）RA共病抑郁症组：每笼饲养1只，关节炎模型建立1周后，给予慢性不可预知温和刺激建立。大鼠处死后腹主动脉采血，采用酶联免疫吸附法测定血清TNF-α、IL-27和5-HT水平。采用方差分析比较组间差异，LSD-t检验进行组间两两比较。

结果

TNF-α和IL-27水平在RA共病抑郁症组均高于正常对照组［（297.97±34.23）ng/L vs （142.31±13.24）ng/L；（297.97±34.73）ng/L vs （212.43±14.52）ng/L］，差异具有统计学意义（t=3.41，P=0.021；t=4.78，P=0.029）。5-HT水平在RA共病抑郁症组低于正常对照组［（108.54±11.51） vs （241.23±13.48）ng/L］，差异具有统计学意义（t=7.821，P=0.017）。

结论

RA共病抑郁症大鼠模型中TNF-α、IL-27水平升高同时伴有5-HT水平降低，提示TNF-α、IL-27和5-HT可能参与了RA共病抑郁症的发病过程，可以作为临床上判断疾病进展及治疗效果的重要参考指标。

关键词: 关节炎，类风湿, 抑郁症, 细胞因子

Objective

To investigate the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-27, and 5-hydroxytryptamine (5-HT) in collagen-induced arthritis (CIA) comorbid with depression.

Methods

A rat model of rheumatoid arthritis (RA) comorbid with depression was established by subjecting type II CIA rats to chronic unpredictable mild stress (CUMS). Thirty-two female Wistar rats were randomly divided into four groups: normal group (four rats per cage, normal feeding), RA group (four rats per cage, normal feeding after modeling), depression group (one rat per cage, CUMS was given to rats), and RA comorbid with depression group (one rat in each cage, CUMS was given one week after the arthritis model was established). Serum TNF-α, IL-27, and 5-HT levels were analyzed by enzyme-linked immunosorbent assay. One-way ANOVA and LSD-t test were used for the overall comparison between groups.

Results

The levels of TNF-α and IL-27 in the model group were significantly higher than those in the control group [(297.97±34.23) ng/L vs (142.31±13.24) ng/L, t=3.41, P=0.021; (297.97±34.73) ng/L vs (212.43±14.52) ng/L, t=4.78, P=0.029]. The levels of 5-HT in the model group was significantly lower than that in the control group [(108.54±11.51) ng/L vs (241.23±13.48) ng/L, t=7.821, P=0.017].

Conclusion

The increase of TNF-α and IL-27 levels and the decrease of 5-HT levels in rats with RA comorbid with depression suggest that TNF- α, IL-27, and 5-HT might be involved in the pathogenesis of RA comorbid with depression. They can be used as important reference indexes to judge the progression of the disease and the therapeutic effect.

Key words: Arthritis, rheumatoid, Depression, Cytokines

表1 各组大鼠TNF-α、IL-27和5-HT水平比较（ng/ml，±s）

组别	数量	TNF-α	IL-27	5-HT
正常组	8	142.31±13.24	212.43±14.52	241.23±13.48
RA组	8	220.15±16.38	258.67±23.17	232.65±14.17
抑郁症组	8	214.83±14.71	238.45±33.08	158.36±12.65
RA共病抑郁症组	8	254.16±19.23^a	297.97±34.73^b	108.54±11.51^c
F值	?	19.62	18.41	12.31
P值	?	<0.001	<0.001	0.023

表1 各组大鼠TNF-α、IL-27和5-HT水平比较（ng/ml，±s）

组别	数量	TNF-α	IL-27	5-HT
正常组	8	142.31±13.24	212.43±14.52	241.23±13.48
RA组	8	220.15±16.38	258.67±23.17	232.65±14.17
抑郁症组	8	214.83±14.71	238.45±33.08	158.36±12.65
RA共病抑郁症组	8	254.16±19.23^a	297.97±34.73^b	108.54±11.51^c
F值	?	19.62	18.41	12.31
P值	?	<0.001	<0.001	0.023

1	石磊，韩晓蕾，石蕊, 等. 类风湿关节炎患者睡眠质量与疾病活动度相关性分析 [J]. 中华风湿病学杂志, 2018, 22(7): 435-439.
2	Cross M, Smith E, Hoy D, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study [J]. Ann Rheum Dis, 2014, 73(7): 1316-1322.
3	Marrie RA, Hitchon CA, Walld R, et al. Increased Burden of Psychiatric Disorders in Rheumatoid Arthritis [J]. Arthritis Care Res, 2018, 70(7): 970-978.
4	Zhang N, Li J, Wang H, et al. The Level of Nesfatin-1 in a Mouse Gastric Cancer Model and Its Role in Gastric Cancer Comorbid with Depression [J]. Shanghai Archives of Psychiatry, 2018, 30(2): 119-126.
5	Brand DD, Latham KA, Rosloniec EF. Collageninduced arthritis [J]. Nat Protoc, 2007, 13(2): 1269-1275.
6	Wang GH, Wu SJ, Wang HL, et al. Plasma Nesfatin-1 concentration and its correlation with HPA axis in depression model rats [J]. J International Psychiatry, 2016, 15(3): 385-388.
7	韩晓蕾，胡风云，石磊, 等. 黄芪与帕罗西汀对抑郁模型小鼠血清IL-18和5-HT影响的研究 [J]. 山西医药杂志, 2015, 44(7): 756-758.
8	Choudhary N, Bhatt LK, Prabhavalkar KS. Experimental animal models for rheumatoid arthritis [J]. Immunopharmacol Immunotoxicol, 2018, 40(3): 193-200.
9	Gibofsky A. Epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis: a synopsis [J]. Am J Manag Care, 2014, 20(5): S128-S135.
10	Chen Z, Bozec A, Ramming A, et al. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis [J]. Nat Rev Rheumatol, 2019, 15(1): 9-17.
11	Fu W, Hu W, Shi L, et al. Foxo4- and Stat3-dependent IL-10 production by progranulin in regulatory T cells restrains inflammatory arthritis [J]. FASEB J, 2016, 31(4): 1354-1367.
12	Abdi E, Najafipour H, Joukar S, et al. Expression of IGF-1, IL-27 and IL-35 Receptors in Adjuvant Induced Rheumatoid Arthritis Model [J]. Iran J Immunol, 2018, 15(1): 14-27.
13	Rajaiah R, Puttabyatappa M, Polumuri SK, et al. Interleukin-27 and interferon-γ are involved in regulation of autoimmune arthritis [J]. J Biol Chem, 2011, 286(4): 2817-2825.
14	McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis [J]. Lancet, 2017, 6(10): 2328-2337.
15	Fearon U. Interleukin-27: A master regulator in inflammation [J]. Arthritis Rheum, 2011, 63(8): 2157-2160.
16	Moon SJ, Park JS, Heo YJ, et al. In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced arthritis [J]. Exp Mol Med, 2013, 45(10): e46.
17	Park J, Jung YO, Oh H, et al. Interleukin-27 suppresses osteoclastogenesis via induction of interferon-γ [J]. Immunology, 2012, 137(4): 326-335.
18	Wesołowska A, Nikiforuk A, Stachowicz K, et al. Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression [J]. Neuropharmacology, 2006, 51(3): 578-586.
19	Pickens SR, Chamberlain ND, Volin MV, et al. Local expression of interleukin-27 ameliorates collagen-induced arthritis [J]. Arthritis Rheum, 2011, 63(8): 2289-2298.
20	Taylor PC, Jain R. The Odd Couple?-Hardly: The emerging overlap between rheumatology and psychiatry [J]. Rheumatology, 2017, 57(8): 1313-1315.
21	Soósová MS, Macejová Ž, Zamboriová M, et al. Anxiety and depression in Slovak patients with rheumatoid arthritis [J]. J Ment Health, 2016, 26(1): 1-7.
22	Ryan S, McGuire B. Psychological predictors of pain severity, pain interference, depression, and anxiety in rheumatoid arthritis patients with chronic pain [J]. Br J Health Psychol, 2016, 21(2): 336-350.
23	Nerurkar L, Siebert S, McInnes IB, et al. Rheumatoid arthritis and depression: an inflammatory perspective [J]. Lancet Psychiatry, 2019, 6(2): 164-173.

[1]	贺敬龙, 尚宏喜, 郝敏, 谢伟, 高明宏, 孙炜, 刘安庆. 重度类风湿关节炎患者行多关节置换术的临床手术疗效[J]. 中华关节外科杂志(电子版), 2023, 17(06): 860-864.
[2]	高玲, 于哲, 范然, 臧银善. 外周血细胞计数比值评估类风湿关节炎疗效的价值[J]. 中华关节外科杂志(电子版), 2023, 17(05): 642-647.
[3]	张曼, 李明庆, 李军苗. 当归四逆汤联合甲氨蝶呤治疗类风湿关节炎的疗效[J]. 中华关节外科杂志(电子版), 2023, 17(05): 648-652.
[4]	刘鹏, 周莹佳, 常彦峰, 甄平, 李生贵, 刘军, 周胜虎. 类风湿关节炎行关节置换围术期风险管理的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(04): 540-548.
[5]	李文金, 薛庆云. 白细胞介素家族炎性细胞因子在骨关节炎中的研究进展[J]. 中华关节外科杂志(电子版), 2023, 17(03): 348-353.
[6]	常洁文, 于亚男, 米亚儒, 邓荷萍. 超声成像技术在膝关节疾病中的应用现状[J]. 中华关节外科杂志(电子版), 2023, 17(03): 404-408.
[7]	陈腊青, 林佳佳, 毛洪刚, 童冠海, 汪梦娜, 夏红波, 刘卓, 徐海霞, 赵玉华, 张传领. 血清细胞因子及呼出气一氧化氮在哮喘-慢性阻塞性肺疾病重叠综合征中的临床意义[J]. 中华危重症医学杂志(电子版), 2023, 16(04): 316-320.
[8]	李敏, 杨凡. 肌细胞因子在儿童肥胖症患儿运动减脂中的作用研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(02): 125-131.
[9]	李芳, 李全, 曹胜军, 王凌峰. 生长因子和细胞因子在创面修复过程中作用的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(02): 174-179.
[10]	李永浩, 高雪菲, 郭田田, 张进, 张彩针, 刘静. 肥胖合并甲状腺癌相关机制的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(04): 311-315.
[11]	沃吟晴, 杨向群. 心脏巨噬细胞的生理功能及在心肌梗死后的作用[J]. 中华细胞与干细胞杂志(电子版), 2023, 13(03): 167-171.
[12]	宋艳, 魏碧霞, 陶勇, 阿依古孜·克里木, 丁琳. 眼内液检测在明确葡萄膜炎病因中应用的临床研究[J]. 中华眼科医学杂志(电子版), 2023, 13(02): 82-87.
[13]	陈蕊, 杨洪娜, 方巍, 李鑫鑫, 李甜甜, 于孝义, 王艳雪, 李文玉. 血清与支气管肺泡灌洗液中细胞因子水平与肺内外ARDS的相关性研究[J]. 中华重症医学电子杂志, 2023, 09(03): 251-258.
[14]	刘立业, 赵德芳. 非酒精性脂肪肝患者血清细胞因子信号转导抑制因子3、肝X受体α水平与CT影像学特征的相关性[J]. 中华消化病与影像杂志(电子版), 2023, 13(04): 211-215.
[15]	潘惠, 王明, 杨忠, 杜向东. 低频重复经颅磁刺激辅助治疗伴不同特征抑郁症的对照研究[J]. 中华临床医师杂志(电子版), 2023, 17(05): 562-568.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Expression characteristics of TNF-α, IL-2, and 5-HT in a model of collagen-induced arthritis comorbid with depression

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Expression characteristics of TNF-α, IL-2, and 5-HT in a model of collagen-induced arthritis comorbid with depression