Study on the treatment of osteoarthritis using sheep model

在第一年，我们试图用绵羊建立骨关节炎(OA)模型。手术切断健康绵羊左侧窒息关节的头十字韧带。每隔4周采集滑液进行生化检查。术后12周和24周处死动物，取窒息关节进行大体和组织学检查，形态观察关节软骨变性、破坏，术后12周骨赘形成。这些形态变化在12~24周内没有出现。生化检查未发现切断韧带的动物与对照动物之间有明显的变化。这些结果表明，颅十字韧带切断后12周时，绵羊膝关节软骨发生了类似骨关节炎的改变，可以作为一种合适的骨关节炎动物模型。第二年，利用绵羊骨关节炎模型，观察了透明质酸和基质金属蛋白酶抑制剂对骨关节炎进展的影响。将绵羊切断颅十字韧带，术后给予生理盐水(生理盐水)、透明质酸关节腔内注射(HA-ia)、透明质酸静脉注射(HA-IV)和基质金属蛋白酶抑制因子静脉注射(MMPI)4种药物治疗11周。经生化和形态检查，各药剂间生化结果无明显差异。与生理盐水相比，HA-IV组软骨的形态变化明显较小。HA-ia的变化较大。略低于氯化钠，但不显著。关节腔内注射透明质酸和静脉注射透明质酸对骨性关节炎的治疗是有效的。

In the first year, we tried to create the osteoarthritis (OA) model using sheep. Cranial cruciate ligaments in the left stifle joint of health sheep were surgically transected. Every 4 weeks, the synovial fluid were collected for biochemical examination. Twelve and twenty-four weeks after surgery, the animals were euthanized and the stifle joints were colelected for macroscopic and histological examination.Morphologically, the cartilage of the joints were degenerated and destructed, and the osteophytosis occurred at 12 weeks after surgery. Those morphological changes did not developed from 12 to 24 weeks. Biochemical examination did not reveal any significant changes between ligament transected animals and control ones.These findings indicated that transaction of the cranial cruciate ligament induced the OA-like-changes of the cartilage in the knee of sheep by 12 weeks, and that this can be a suitable OA animal model.In the second year, using the sheep OA model, the effects of hyaluronan and matrix metalloproteinase inhibitor on OA progress were examined. Sheep, whose cranial cruciate ligament were transected, were administered the following 4 agents for 11 weeks after surgery ; saline iv (NaCl), hyaluronan intra articular (HA-ia), hyaluronan iv (HA-iv) and matrix metalloproteinase inhibitor iv (MMPI). Biochemical and morphological examination were performed.No significant deference were found in the biochemical results between the agents. Morphologically, the change of the cartilage in HA-iv was significantly small compared to NaCl. The change in HA-ia was more. slight than NaCl, but it was not significant. The cartilage in MMPI was destroyed to the same degree as NaCl.These findings indicated that the hyaluronan administration both intra-articular and intravenous were effective as the treatment for OA.