A modified rabbit model of gouty knee arthritis

doi:10.3969/j.issn.2095-4344.2017.24.019

Abstract

Abstract:

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.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Arthritis, Knee Jpint, Models, Animal, Gout, Tissue Engineering

CLC Number:

R318

Li Qi, Chen Xu-xu, Li Jian. A modified rabbit model of gouty knee arthritis[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(24): 3881-3887.

Figures/Tables 3

2.3 关节肿胀指数术后各个组关节肿胀指数的随时间的变化见图1。可以看出，经典模型组和改良模型组术后关节肿胀指数立即增高，在术后第1或2天达到高峰，其后均开始下降，经典模型组下降较迅速，于术后第3周时已趋于正常，与空白对照组相比无明显差异(P=0.371)；而改良模型组下降较缓慢，术后第4周时与空白对照组相比存在显著性差异(P=0.017)。与空白对照组相比，经典模型组(P=0.007)和改良模型组(P=0.001)关节肿胀指数的整体变化趋势均有显著性差异。在术后2周内经典模型组的关节肿胀指数均显著性高于空白对照组，而改良模型组在术后4周内均高，且差异有统计学意义。假手术组，关节肿胀指数在术后1-3 d内亦有轻度的增高，但是到术后1周时基本趋于正常，整体变化趋势与空白对照组相比无显著性差异(P=0.122)。改良模型组与假手术组相比，关节肿胀指数的整体变化趋势存在显著性差异(P=0.030)，在术后4周内改良模型组均显著性高于假手术组。 2.4 大体观察术后2周时，4组兔膝关节病理学改变大体情况可见图2。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，较肥厚，伴充血水肿；关节腔内有较多量关节液形成；周围组织充血水肿；软骨未见明显破坏。此外，改良模型组关节内可见较多量的尿酸盐结晶，被增生的滑膜组织所包裹(图2D)；经典模型组关节滑膜内亦可见散在的尿酸盐结晶(图2C)，但总量与改良组相比明显较少。 2.5 血清、关节液中白细胞介素6和白细胞介素1β的水平 2.5.1 血清、关节液中白细胞介素6 4组间不同时间点血清中白细胞介素6的水平见表3。图3A显示术后各组血清中白细胞介素6水平随时间的变化。可以看出，经典模型组和改良模型组术后血清白细胞介素6水平立即增高，分别在术后第1和第2天达到高峰，其后均开始下降，经典模型组下降较迅速，于术后第3周时已趋于正常；而改良模型组下降较缓慢，术后第3和4周时与经典模型组相比存在显著性差异(分别为P=0.041和P=0.005)。与空白对照组相比，经典模型组(P=0.013)和改良模型组(P=0.027)血清白细胞介素6水平的整体变化趋势均有显著性差异。在术后4周内改良模型组的白细胞介素6水平均显著性高于空白对照组。假手术组，血清白细胞介素6水平在术后1-3 d内亦有轻度的增高，但是到术后1周时基本趋于正常，整体变化趋势与空白对照组相比无显著性差异(P=0.078)。改良模型组与假手术组相比，血清白细胞介素6水平的整体变化趋势存在显著性差异(P=0.040)，在术后4周内各个时间点改良模型组均显著性高于假手术组。图3B显示术后各个组关节液中白细胞介素6水平随时间的变化。可以看出，经典模型组和改良模型组术后1周时关节液白细胞介素6水平较高，其后均开始下降，经典模型组下降较迅速，于术后第3周时已趋于正常；而改良模型组下降较缓慢，术后第4周时与空白对照组相比亦然存在显著性差异(P=0.010)。在术后4周内改良模型组的白细胞介素6水平均显著性高于空白对照组。假手术组，关节液白细胞介素6水平在术后2周内亦显著性增高，但是到术后3周时基本趋于正常，整体变化趋势与空白对照组相比无显著性差异(P=0.193)。改良模型组与假手术组相比，关节液白细胞介素6水平的整体变化趋势存在显著性差异(P=0.032)，在术后4周内各个时间点改良模型组均显著性高于假手术组。 2.5.2 血清、关节液中白细胞介素1β的水平 4组间不同时间点血清中白细胞介素1β水平的情况见表4。图3C显示术后各个组血清中白细胞介素1β水平的随时间的变化。可以看出，经典模型组和改良模型组术后血清白细胞介素1β水平立即增高，分别在术后第1和第2天达到高峰，其后均开始下降，经典模型组下降较迅速，于术后第3周时已趋于正常；而改良模型组下降较缓慢，术后第3和第4周时与经典模型组相比差异存在显著性意义(分别为P=0.037和P=0.027)。与空白对照组相比，经典模型组(P=0.010)和改良模型组(P=0.022)血清白细胞介素1β水平的整体变化趋势均有显著性差异。在术后4周内改良模型组的白细胞介素1β水平均显著性高于空白对照组。假手术组，血清白细胞介素1β水平在术后1-3 d内亦有轻度的增高，但是到术后1周时基本趋于正常。改良模型组与假手术组相比，血清白细胞介素1β水平的整体变化趋势存在显著性差异(P=0.039)，在术后4周内各个时间点改良模型组均显著性高于假手术组。图3D显示术后各个组关节液中白细胞介素1β水平的随时间的变化。可以看出，经典模型组和改良模型组术后1周时关节液白细胞介素1β水平较高，其后均开始下降，经典模型组下降较迅速，于术后第3周时已趋于正常；而改良模型组下降较缓慢，术后第3和第4周时与经典模型组相比存在显著性差异(分别为P=0.043和P=0.016)。在术后4周内改良模型组的白细胞介素1β水平均显著性高于空白对照组。假手术组，关节液白细胞介素1β水平在术后1周内亦显著性增高，但是到术后2周时基本趋于正常，整体变化趋势与空白对照组相比无显著性差异(P=0.087)。改良模型组与假手术组相比，关节液白细胞介素1β水平的整体变化趋势存在显著性差异(P=0.029)，在术后4周内各个时间点改良模型组均显著性高于假手术组。"

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