Study on the treatment of osteoarthritis using sheep model

在第一年，我们尝试用绵羊建立骨关节炎（OA）模型。手术切断健康绵羊左后膝关节前交叉韧带。每4周采集关节液进行生化检查。术后12周和24周分别处死动物，取膝关节进行大体和组织学检查，术后12周关节软骨发生变性破坏，出现骨赘。12 ~ 24周未见明显形态学改变。实验结果表明，前交叉韧带切断后12周，绵羊膝关节软骨出现OA样改变，可作为一种较理想的OA动物模型。观察透明质酸和基质金属蛋白酶抑制剂对OA进展的影响。绵羊，其颅侧交叉韧带被切断，在手术后给予以下4种药剂11周：生理盐水iv（NaCl）、透明质酸关节内（HA-ia）、透明质酸iv（HA-iv）和基质金属蛋白酶抑制剂iv（MMPI）。结果表明，两种制剂的生化指标无显著性差异。在形态学上，HA-iv中软骨的变化明显小于NaCl。在哈-亚的变化更多。比NaCl稍弱，但不显著。MMPI中软骨的破坏程度与NaCl相同，提示关节内和静脉注射透明质酸治疗OA均有效。

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.