雌性Lewis大鼠佐剂诱导关节炎模型的建立与评价

Establishment and evaluation of adjuvant-induced arthritis model in female Lewis rats

目的建立佐剂诱导关节炎(adjuvant-induced arthritis,AA)大鼠模型及其评价方法。方法将20只雌性Lewis大鼠随机分为AA模型组和对照组,每组10只。在模型组大鼠右后足趾皮内注射完全弗氏佐剂(complete Freund’s adjuvant,CFA)建立AA模型,对照组则注射生理盐水。通过动物体质量、机械痛阈(mechanical withdraw threshold,MWT)、后足容积、关节炎指数(arthritis index,AI)评分及全血白细胞计数(white blood cell count,WBC)和血沉(erythrocyte sedimentation rate,ESR)等指标对模型进展进行评价。分别在建模后第14,28天取材进行踝关节组织病理学检查,并测定大鼠肝脏、脾脏及胸腺质量对于体质量的相对质量。结果AA模型大鼠注射CFA后可出现多发性关节炎,其病程呈阶段性特点。注射后第1-14天为急性期及相对缓解期,主要表现为注射足机械痛阈降低(P<0.001)、足容积增加(P<0.001)以及AI评分的升高(P<0.001),血液学检查可见WBC升高(P<0.001)和ESR加快(P<0.001);至建模第14天时模型大鼠肝脏(P<0.01)、脾脏(P<0.05)及胸腺(P<0.05)相对质量均显著高于对照组,注射足踝关节HE染色则以炎症表现为主;第15-28天为模型病程进展的慢性期,特征性表现为开始出现对侧足的疼痛(P<0.05)和肿胀(P<0.05),此阶段AI评分进一步升高(P<0.001),体质量减轻(P<0.05),WBC与ESR水平仍显著高于对照组(P<0.001),注射足踝关节出现结构的破坏。结论成功建立了AA大鼠模型及模型的评价方法。

Objective To establish a rat model of adjuvant-induced arthritis(AA)and a method for its evaluation.Methods Twenty female Lewis rats were randomly divided into AA model group and control group,with 10 rats in each group.The AA model was established by intracutaneous injection of complete Freund’s adjuvant(CFA)into the right hind paw,while the rats in control group were injected with normal saline.The progress of the model was evaluated by body weight,mechanical withdrawal threshold(MWT),hind paw volume,arthritis index(AI)score,as well as hematological examinations including white blood cell count(WBC)and erythrocyte sedimentation rate(ESR).The ankle joint histological examination were performed at 14 d and 28 d after immunization,and organ weights were determined.Results Rats with AA developed multiple arthritis after injection of CFA,and the course of disease was characterized by stages.At 1-14 d after injection of CFA(the acute phase and relative remission stages),MWT was decreased(P<0.001),while the volume of the injection hind paw and AI score were increased(P<0.001),and the hematological examination showed the increase of WBC and the acceleration of ESR(P<0.001).The relative ratio of liver(P<0.01),spleen(P<0.05)and thymus(P<0.05)to body weight were higher in model group than in control group at 14 d,while HE staining of ankle joint mainly showed inflammation.At 15-28 d after injection of CFA(the chronic phase),the model was characterized by the onset of pain and swelling of the contralateral hindpaws(P<0.05),the AI score was further increased(P<0.001)accompanied with the loss of body weights(P<0.05),and the levels of WBC and ESR were still significantly higher in model group than in control group(P<0.001).The histological examination showed the structural destruction in ankle joint of injected hind paw at 15-28 d.Conclusion The AA model and its evaluation methods are successfully established in rats.