摘要
目的:建立急性痛风性关节炎动物模型,探索尿酸钠(monosodium urate, MSU)晶体的最佳诱导条件及炎症反应特点.方法:以改进方法制备MSU晶体,通过Wistar大鼠单侧踝关节注入50 μl不同浓度的MSU晶体诱导急性单关节炎,研究关节炎性变化与注入MSU剂量的关系;观测诱导关节炎后不同时间点的炎症指数、肿胀指数和功能障碍指数变化.结果:改进制备的MSU晶体呈骨针形,大小一致.5 mg/ml的MSU可导致明显的关节红肿.5～20 mg/ml范围内,关节红肿和功能障碍严重程度呈剂量依赖性增加,超过20 mg/ml后关节炎的严重程度不再随MSU注射用量的增加而加重,但可延长关节炎病程,并见关节腔内MSU晶体被大量蛋白样物质和炎性细胞包裹.将20 mg/ml的MSU注入大鼠踝关节可见迅速出现关节红肿和功能障碍,发生率100%;诱导后2 h出现,4 h表现明显,8～12 h达高峰期,24 h后自发减轻,5～6 d自行缓解;关节炎高峰期见三足步态,组织严重水肿,关节腔明显积液;关节液、关节滑膜及其周围组织见大量炎性细胞浸润,较好地模拟了人急性痛风性关节炎的病变特点.结论:改进方法制备的晶体提高了实验可重复性,并可成功诱导典型的大鼠急性关节炎.MSU剂量以每个踝关节20 mg/ml×50 μl为最佳.该模型适合于痛风的相关实验研究.
Objective： To establish and identify a rat model of acute arthritis induced by monosodium urate （MSU.） monohydrate crystal. Methods： MSU monohydrate crystals were prepared according to the documented method with some modifications. Different doses of MSU were injected into unilateral ankle of rat, and the relationships between the MSU dosages and inflammatory reactions in the joint were studied. In the 1 mg of MSU monohydrate crystal induced arthritis, joint inflammatory index, swelling index and disability index, as well as pathological changes in synovium were systematically assessed after stimulation for increasing periods of time. Results： Preparation of MSU monohydrate crystals with modified method produced bone spicule-shaped crystals with even shape and size. 0.25 mg or above of MSU induced markedly acute arthritis in rat. The severity of arthritis was dose-dependently increased by MSU at doses from 0.25 mg to 1 mg, but it no more increased as the doses of MSU were above 1 mg. However, more MSU resulted in a longer course of arthritis. Furthermore, MSU in joint cavity was found coated with inflammatory cells and protein-like substance. Injection with 1 mg of MSU into rat ankle joint cavity triggered acute arthritis with incidence of 100%. Visible arthritis occurred with red swelling and dysfunction at 2 hours after injection, and the severity of arthritis markedly rose at 4 hours, reached the peak phase at 10 （8 - 12） hours, declined after 24 hours, and then spontaneously recovered after 5 to 6 days. At the peak of arthritis, the rats showed tri-legged gait, and severe edema in the tissue, as well as hydrarthrosis with massive leukocytes infiltrating into joint cavity and the tissue around. Conclusion： MSU crystals prepared by modified method could induce acute arthritis and enhance the experimental repeatability. The optimum dose of MSU for induction of acute arthritis is 1 mg （20 mg/ml · 50μl） per ankle cavity. The model mimickes well the key characteristics of human gouty arthritis and is appropriate for experimental research on gouty arthritis.
出处
《军事医学科学院院刊》
CSCD
北大核心
2005年第6期538-542,共5页
Bulletin of the Academy of Military Medical Sciences
基金
军事医学科学院创新启动基金资助项目(YC0216)
关键词
尿酸钠晶体
痛风
关节炎
动物模型
大鼠
monosodium urate monohydrate crystal
gout
arthritis
animal model
rats
