Cashin C H, Doherty N S, Jeffries B L, Buckland-Wright J C
Br J Exp Pathol. 1980 Jun;61(3):296-302.
Guinea-pigs were sensitized by intra-articular injection of M. tuberculosis (2.0 mg) into one knee joint and arthritis induced in the opposite knee 21 days later by intra-articular injection of antigen (0.2 mg). The time course off the arthritic changes was followed for 25 days by assessment of knee swelling and hind-limb flexion. Twenty-eight days after challenge the experiment was terminated and radiographic changes evaluated by means of a microfocal X-ray unit. The effect of treatment with the anti-rheumatic drugs, D-penicillamine (100 mg/kg by mouth), dexamethasone (0.1 mg/kg i.p.), aspirin (100 mg/kg by mouth), chloroquine phosphate (30 mg/kg by mouth) and sodium aurothiomalate (2 mg/kg i.m.) given daily from 10 days after sensitization until 28 days after challenge was assessed. Changes in joint swelling and hind-limb flexion were maximal 1-3 days after challenge. None of the drug treatments influenced these parameters. Microfocal radiography showed marked changes in arthritis animals of all X-ray parameters measured. It was possible readily to identify joint erosion, trabecular loss and associated osteoporosis, the latter occurring proximal to and relatively remote from the affected joint. None of the treatments prevented the radiographic changes but exacerbation of trabecular number in the area of the epiphysis was seen with aspirin and D-penicillamine and of trabecular density further up the shaft of the femur was seen with D-penicillamine. The changes with D-penicillamine may reflect the potentiation of cell-mediated hypersensitivity with this drug reported by other workers. It was concluded that the model is not suitable for the detection of clinically active anti-rheumatic drugs but that microfocal radiography provides a sensitive index for the assessment of joint damage in small animals.
通过向豚鼠的一个膝关节内注射2.0毫克结核分枝杆菌使其致敏,21天后通过向对侧膝关节内注射0.2毫克抗原诱导关节炎。通过评估膝关节肿胀和后肢屈曲情况,对关节炎变化的时间进程进行了25天的跟踪。激发后28天终止实验,并用微焦点X射线装置评估放射学变化。评估了从致敏后10天至激发后28天每天给予抗风湿药物D-青霉胺(口服100毫克/千克)、地塞米松(腹腔注射0.1毫克/千克)、阿司匹林(口服100毫克/千克)、磷酸氯喹(口服30毫克/千克)和金硫代苹果酸钠(肌肉注射2毫克/千克)的治疗效果。激发后1 - 3天关节肿胀和后肢屈曲的变化最大。没有一种药物治疗影响这些参数。微焦点放射摄影显示所有测量的X射线参数在关节炎动物中都有明显变化。很容易识别出关节侵蚀、小梁丢失和相关的骨质疏松,后者发生在受影响关节的近端和相对较远的部位。没有一种治疗方法能阻止放射学变化,但阿司匹林和D-青霉胺可使骨骺区域的小梁数量增加,D-青霉胺可使股骨骨干上部的小梁密度增加。D-青霉胺的这些变化可能反映了其他研究者报道的该药物对细胞介导的超敏反应的增强作用。得出的结论是,该模型不适用于检测临床上有活性的抗风湿药物,但微焦点放射摄影为评估小动物的关节损伤提供了一个敏感指标。