一种改良膝关节痛风性关节炎兔模型

A modified rabbit model of gouty knee arthritis

背景:良好的动物模型是研究痛风性关节炎重要的实验方法和手段。然而,目前尚无十分理想的痛风性关节炎动物模型,这给寻找新的药物、方法治疗痛风性关节炎带来阻碍。目的:评价改良后的兔膝关节痛风模型的有效性。方法:选取新西兰大白兔随机分成4组。空白对照组不做任何处理,右膝作为观察侧;假手术组取大网膜,处理后不包裹单钠尿酸盐结晶,单纯将大网膜植入兔右侧膝关节髌上囊腔;经典模型组将单钠尿酸盐结晶混悬液(0.1 g/L)注射入兔右侧膝关节髌上囊腔;改良模型组取大网膜,处理后包裹单钠尿酸盐结晶(100 mg/kg),植入兔右侧膝关节髌上囊腔。观察造模后1,2,3 d及造模后1,2,3,4周关节肿胀程度、活动情况及关节炎症反应等来评估改良模型的优缺点。结果与结论:(1)造模后4周内各个时间点改良模型组的兔关节功能均显著降低(P<0.05);(2)经典模型组和改良模型组造模后关节肿胀指数分别在造模后第1或2天达到高峰,其后均开始下降,而改良模型组较经典模型组下降缓慢,造模后第4周时与空白对照组相比存在显著性差异;(3)大体观察:改良模型组和经典模型组均呈现出明显的关节炎症改变:滑膜广泛增生,伴充血水肿;关节腔内有较多关节液形成;周围组织充血水肿;软骨未见明显破坏;(4)经典模型组和改良模型组造模后血清和关节液中白细胞介素6及白细胞介素1β水平分别在术后第1和第2天达到高峰,其后均开始下降,改良模型组下降较经典模型组缓慢,至造模后4周时仍高于其他3组(P<0.05);(5)结果说明,通过向兔膝关节腔内植入用自体大网膜包裹的单钠尿酸盐结晶可以成功地制造兔膝关节痛风性关节炎的模型,模型可维持至4周以上,较经典模型维持时间显著延长。

BACKGROUND： An ideal animal model is important for studying gouty arthritis. However, a lack of perfect animal model of gouty arthritis delays the progress in searching for a novel drug and treatment method. OBJECTIVE： To evaluate the effectiveness of the modified rabbit model of gouty knee arthritis. METHODS： New Zealand white rabbits were selected and randomly divided into four groups. Except blank control group received no intervention; the rabbit greater omentum was removed, which was wrapped with nothing （sham operation group）, implanted with 0.1 g/L monosodium urate crystal suspension （conventional group）, or 100 mg/kg monosodium urate crystal （modified group） into the suprapatellar cyst of the rabbit right knee. The swelling degree, motor function, and inflammatory response of the knee joint were observed at 1, 2 and 3 days, 1, 2, 3, and 4 weeks after modeling to evaluate the advantages and disadvantages of the modified model. RESULTS AND CONCLUSION： The movement function in the modified group was significantly decreased within 〈 weeks after modeling （P 〈 0.05）. The joint swelling index in the conventional and modified groups peaked on day 1 or 2, and then began to decrease. The descent velocity in the modified group was slower than that in the conventional group, and the swelling index showed significant difference between modified and blank control groups at 4 weeks after modeling （P 〈 0.05）. The conventional and modified groups presented with overt inflammatory response, synovial hyperplasia, congestion and edema; abundant synovial fluid appeared in the articular cavity; periphery tissue became congestion and edema; the cartilage revealed no obvious damage. The levels of interleukin-6 and -1β in serum and synovial fluid in the conventional and modified groups peaked on days 1 and 2, followed by a decrease, but the modified group exhibited a slower descent velocity compared with the modified group. All above levels in the modified group were significantly higher than those in the other three groups （P 〈 0.05）. These results suggest that the rabbit model of gouty knee arthritis is successful established by the intra-articular implantation with the autogenous greater omentum-wrapped monosodium urate crystal, which can last more than 4 weeks, longer than the conventional model.