Study on the treatment of osteoarthritis using sheep model

在第一年，我们尝试用羊来创建骨关节炎（OA）模型。对健康羊左膝关节的颅交叉韧带进行了手术切除。每4周采集滑液进行生化检查。术后12周和24周，对大鼠实施安乐死，取大鼠膝关节进行肉眼和组织学检查。形态学上，关节软骨退行性破坏，术后12周出现骨赘。这些形态变化在12 ~ 24周内没有发生。生化检查未发现韧带横断动物与对照组有明显变化。这些结果表明，颅交叉韧带的交易在12周时诱导了羊膝关节软骨的OA样变化，可以作为一种合适的OA动物模型。第二年，采用羊OA模型，研究了透明质酸和基质金属蛋白酶抑制剂对OA进展的影响。切除颅十字韧带的绵羊，术后11周给予以下4种药物；盐水iv （NaCl）、关节内透明质酸（HA-ia）、透明质酸iv （HA-iv）和基质金属蛋白酶抑制剂iv （MMPI）。进行生化和形态学检查。两剂间的生化结果无显著差异。形态学上，HA-iv对软骨的改变明显小于NaCl。HA-ia的变化更多。略高于NaCl，但不显著。MMPI对软骨的破坏程度与NaCl相同。这些结果表明，关节内和静脉注射透明质酸是治疗OA的有效方法。

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.