建立并评价类风湿关节炎（RA）共病抑郁症动物模型。

通过复合造模思路，在Ⅱ型胶原诱导关节炎（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RA共病抑郁症大鼠模型。采用糖水消耗和旷场测试进行大鼠行为学测定。采用酶联免疫吸附法（ELISA）测定外周血清IL-27、IL-17和IL-10水平。采用单因素方差分析比较大鼠体质量、糖水饮用量、旷场实验得分以及血清因子水平的差异，组间两两比较采用LSD-t检验。

RA共病抑郁症组大鼠踝关节肿大、畸形，伴有运动迟缓、快感缺乏等抑郁状态。造模后第28天时大鼠体质量方面抑郁症组［（63.6±2.5）g］、RA共病抑郁症组［（152.2±3.2）g］均低于正常对照组［（179.5±3.7）g］，差异均有统计学意义（t=-2.383，P=0.019；t=-3.887，P=0.010）。慢性应激刺激后第22天时，大鼠饮用糖水量方面抑郁症组［（19.8±0.3）g］、RA共病抑郁症组［（18.9±0.1）g］明显小于正常对照组［（31.7±0.8）g］，差异具有统计学意义（t=6.71，P=0.016；t=5.12，P=0.023）。抑郁症组大鼠刺激后旷场实验水平得分、垂直得分均低于正常对照组［（54.41±6.42）分vs（98.34±4.83）分；（19.83±2.31）分vs（36.03±2.75）分］，差异均有统计学意义（t=5.31，P=0.023；t=2.34，P=0.042）。RA共病抑郁症组大鼠刺激后水平得分、垂直得分均低于正常对照组［（38.35±3.28）分vs（98.34±4.83）分；（12.73±3.42）分vs（36.03±2.75）分］，差异均有统计学意义（t=3.96，P=0.032；t=3.26，P=0.035）。IL-27、IL-17和IL-10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 （212.43±14.52）ng/L；（184.62±33.71）ng/L vs （109.40±9.81）ng/L；（162.74±25.38）ng/L vs （131.51±20.43）ng/L ］，差异均具有统计学意义（t=4.78，P=0.0291；t=2.57，P=0.032；t=5.33，P=0.023）。

RA共病抑郁症组大鼠模型符合临床上RA共病抑郁症患者特征，该模型具有重复性高、易操作特点，是研究RA共病抑郁症理想动物模型。

To establish and evaluate an animal model of rheumatoid arthritis (RA) comorbid with depression.

A rat model of RA comorbid with depression was established based on a model of type II collagen-induced arthritis (CIA) combined with chronic unpredictable mild stress. Evaluation of mice behavior was performed by the Open-field test and sucrose preference test. Serum IL-27, IL-17, and IL-10 levels were determined by ELISA. One-way ANOVA and LSD-t test were used for the overall comparison between groups.

The ankle joints of rats in the model group were swollen and deformed, accompanied with retardation of movement and lack of pleasure. On the 28th day after modeling, the body mass of rats in the depression alone group [(63.6±2.5) g vs (179.5±3.7) g, F=7.64] and comorbidity group [(152.2±3.2) g vs (179.5±3.7) g, F=12.37] was significantly lower than that of the normal control group (t=-2.383, P=0.019; t=-3.887, P=0.010). On the 22nd day after chronic stress stimulation, the intake of sugar water in the depression alone group [(19.8±0.3) g vs (31.7±0.8) g] and comorbidity group [(18.9±0.1) g vs (31.7±0.8) g, F=26.71] was significantly lower than that of the normal control group (t=6.71, P=0.016; t=5.12, P=0.023). The horizontal score [(54.41±6.42) points vs (98.34±4.83) points] and vertical score [(19.83±2.31) points vs (36.03±2.75) points] in the depression alone group after stimulation were significantly lower than those of the normal control group (t=5.31, P=0.023; t=2.34, P=0.042). The horizontal score [(38.35±3.28) points vs (98.34±4.83) points] and the vertical score [(12.73±3.42) points vs (36.03±2.75) points, F=7.31] of the comorbidity group were significantly lower than those of the normal control group (t=3.96, P=0.032; t=3.26, P=0.035). The levels of IL-27, IL-17, and IL-10 in the model group [(297.97±34.23) ng/L vs (212.43±14.52) ng/L; (184.62±33.71) ng/L vs (109.40±9.81) ng/L; (162.74±25.38) ng/L vs (131.51±20.43) ng/L] were significantly higher than those in the control group (t=4.78, P=0.0291; t=2.57, P=0.032; t=5.33, P=0.023).

The comorbidity group rats showed typical characteristics of arthritis and depression, such as ankle swelling, deformity, and lack of pleasure. The above symptoms are consistent with the clinical characteristics of patients with RA comorbid with depression. The model has high reproducibility and is easy to operate, and it is an ideal model for the study of RA combined with depression.