Cai X, Wong Y F, Zhou H, Xie Y, Liu Z Q, Jiang Z H, Bian Z X, Xu H X, Liu L
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, People's Republic of China.
Naunyn Schmiedebergs Arch Pharmacol. 2006 May;373(2):140-7. doi: 10.1007/s00210-006-0062-5. Epub 2006 Apr 26.
The outbred Sprague-Dawley (SD) rats, similar to the inbred Lewis (LEW) rats, have been recently demonstrated to be highly susceptible to adjuvant-induced arthritis (AIA). We herein compared AIA in SD and LEW rats in terms of clinical, histological, radiological, and immuno-inflammatory features. The results showed that, following inoculation with a ground Mycobacterium tuberculosis (MT) suspension, SD and LEW rats manifested closely similar disease progression, with 100% incidence and similar severity. The development of arthritis was accompanied by significantly higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels than in control rats. Radiographic examination of the hind paws showed that both SD and LEW AIA rats manifested conspicuous soft tissue swelling, bone matrix resorption, periosteal new bone formation and bone erosion, while histopathological analysis of the synovial joints revealed marked cellular infiltration, angiogenesis, synovial hyperplasia, pannus formation, narrowing of joint space, and cartilage and bone destruction. Moreover, in relation to disease progression, serum tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 levels were markedly overexpressed in both SD and LEW AIA versus control rats, and SD and LEW AIA rats exhibited divergent profiles for the expression of TNF-alpha and IL-1beta. Taken together, these results demonstrated that the SD rat AIA model shares several arthritic features with the comparable model in LEW rats. Hence, given the more favorable characteristics of SD rats than LEW rats (i.e., lower cost, wider availability, and heterogenic background), this SD rat AIA model is more cost effective and advantageous for screening and testing novel anti-arthritic agents.
与近交系Lewis(LEW)大鼠相似,远交系Sprague-Dawley(SD)大鼠最近被证明对佐剂性关节炎(AIA)高度敏感。我们在此比较了SD和LEW大鼠AIA在临床、组织学、放射学和免疫炎症特征方面的情况。结果表明,接种结核分枝杆菌(MT)悬液后,SD和LEW大鼠表现出非常相似的疾病进展,发病率均为100%,严重程度相似。关节炎的发展伴随着红细胞沉降率(ESR)和C反应蛋白(CRP)水平显著高于对照大鼠。对后爪的放射学检查显示,SD和LEW AIA大鼠均表现出明显的软组织肿胀、骨基质吸收、骨膜新骨形成和骨侵蚀,而滑膜关节的组织病理学分析显示有明显的细胞浸润、血管生成、滑膜增生、血管翳形成、关节间隙变窄以及软骨和骨破坏。此外,就疾病进展而言,与对照大鼠相比,SD和LEW AIA大鼠血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和IL-6水平均明显过度表达,并且SD和LEW AIA大鼠在TNF-α和IL-1β表达方面表现出不同的特征。综上所述,这些结果表明SD大鼠AIA模型与LEW大鼠的类似模型具有一些关节炎特征。因此,鉴于SD大鼠比LEW大鼠具有更有利的特性(即成本更低可用性更广且背景异质性),该SD大鼠AIA模型在筛选和测试新型抗关节炎药物方面更具成本效益且更具优势。