类风湿关节炎贫血大鼠模型的建立及评价

Establishment and Evaluation of Anemia Rat Models Associated by Rheumatoid Arthritis

目的建立类风湿关节炎贫血(rheumatoid arthritis and anemia,RA-A)的大鼠模型,为进一步研究其机制和治疗提供良好的动物模型。方法选用雄性Wistar大鼠30只,体重150~170 g,随机分为正常对照组、模型Ⅰ组和模型Ⅱ组,各10只。正常对照组在大鼠左后肢足趾注射生理盐水0.625 ml/kg;模型Ⅰ组同一部位注射2.5 mg/ml的Ⅱ型胶原1.5 ml与5 ml弗氏完全佐剂乳化的乳化液0.625 ml/kg;模型Ⅱ组在模型Ⅰ组的基础上,于大鼠左侧大腿肌肉注射肿瘤坏死因子-α(TNF-α)1.25μg/kg构建大鼠模型。分别测定干预后不同时间点血液中红细胞计数(RBC)、血红蛋白(HGB)以关节肿胀度和大鼠体重;并于造模第39天,检测血清白介素-6(IL-6)、IL-1、TNF-α、干扰素-γ(IFN-γ)含量及大鼠关节软骨组织病理学变化。结果造模第2、5、10、17和39天模型Ⅰ组和Ⅱ组体重低于正常对照组(P<0.01),踝关节肿胀度均高于正常对照组(P<0.01)。造模第10、17和39天,模型Ⅱ组RBC和HGB均低于正常对照组和模型Ⅰ组(P<0.01),且模型Ⅰ组均低于正常对照组(P<0.01)。造模第39天,模型Ⅱ组IL-6、IL-1、TNF-α和IFN-γ水平均高于正常对照组和模型Ⅰ组(P<0.01),且模型Ⅰ组均高于正常对照组(P<0.01)。模型Ⅱ组关节软骨组织病理损伤较正常对照组和模型Ⅰ组严重。结论本研究方法成功获得RA-A的动物模型,是适合研究RA-A发病机制及其治疗的模型。

Objective To establish rat models of rheumatoid arthritis and anemia （RA-A） to provide a good animal model for further study on pathogenesis and treatment of RA-A. Methods A total of 30 male Wistar rats with 150- 170g body weight were randomly divided into control, model I and model Ⅱ groups （n = 10 for each group）. Control group was injected with 0. 625 ml/kg physiological saline at the left hind toe; model I group was injected with 1.5 ml solution of 2.5 mg/ml 11 collagen and 5 ml freund complete adjuvant emulsion of 0. 625 ml/kg at the same injection site with control group ; model Ⅱ group was intramuscularly injected with 1.25 p.g/kg tumor necrosis factor-or （TNF-ot） at left muscles of thigh on the basis of treatment for model I group. Values of red blood cell count （RBC） , hemoglobin （ HGB）, degree of joint swelling and rat weight at different time points after intervention were respectively detected. Contents of serum interleukin-6 （ IL-6）, IL-1, TNF-α, interferon-7 （IFN-γ） and histopathological changes of articular cartilage in rats were also detected at the 39th days after model establishment. Results At the 2nd , 5th, 10th , 17th and 39th days after model establishment, values of weight were significantly lower （P 〈 0. 01 ） , while degree values of joint swelling were significantly higher in model Ⅰand Ⅱ groups than those in control group （P 〈 0. 01 ）. At the 10th , 17th and 39th days after model establishment, RBC and HGB values in model Ⅱ group were significantly lower than those in control and model I groups （P 〈 0.01 ） , and the values in model I group were significantly lower than those in control group （ P 〈 0. 01 ）. At the 39th day after model establishment, IL-6, IL-1, TNF-α and IFN-γ contents in model Ⅱ group were significantly higher than those in control and model I groups （P 〈 0.01 ） , and the contents in model group I were significant- ly higher than those in control group （P 〈 0. 01 ）. Histopathological damage degree of articular cartilage in model Ⅱ group was severe than those in control and model I groups. Conclusion RA-A rat models can be successfully obtained by the method in this study, and it is an ideal model for studying pathogenesis and treatment of RA-A.