Brandt K D, Smith G, Kang S Y, Myers S, O'Connor B, Albrecht M
Rheumatology Division, Indiana University School of Medicine, Indianapolis 46202-5103, USA.
Osteoarthritis Cartilage. 1997 Nov;5(6):438-49. doi: 10.1016/s1063-4584(97)80048-9.
To determine whether diacerhein has a disease-modifying effect in an accelerated canine model of osteoarthritis.
Fourteen adult mongrel dogs underwent unilateral L4-S1 dorsal root ganglionectomy (DRG), followed 3 weeks later by ipsilateral anterior cruciate ligament transection. Seven dogs received diacerhein (15-20 mg/kg) daily throughout the interval between DRG and sacrifice, eight weeks after ligament transection. The other seven dogs served as OA controls.
The mean volume of synovial fluid obtained from the OA knee of the diacerhein-treated dogs was approximately 40% less than that from the OA knee of the controls. In addition, diacerhein appeared to reduce the severity of fibrillation (femoral condyle) and full-thickness ulceration (trochlear ridge) of the articular cartilage and the level of collagenase activity in extracts of the OA cartilage, and to increase net PG synthesis in the OA cartilage, although none of the above changes were statistically significant.
The differences between the diacerhein group and untreated OA controls, even though not statistically significant, suggest that diacerhein was active in this rapidly progressive model of OA. Because changes associated with initiation of OA may be different than those associated with progression, whether diacerhein has a disease-modifying effect should be examined in a less rapidly progressive model.
确定双醋瑞因在犬类骨关节炎加速模型中是否具有改善病情的作用。
14只成年杂种犬接受单侧L4 - S1背根神经节切除术(DRG),3周后进行同侧前交叉韧带横断术。在韧带横断术后8周,即DRG至处死期间,7只犬每日接受双醋瑞因(15 - 20毫克/千克)治疗。另外7只犬作为骨关节炎对照组。
从接受双醋瑞因治疗的犬的骨关节炎膝关节获取的滑液平均体积比对照组犬的骨关节炎膝关节的滑液平均体积少约40%。此外,双醋瑞因似乎降低了关节软骨的纤维化(股骨髁)和全层溃疡(滑车嵴)的严重程度以及骨关节炎软骨提取物中的胶原酶活性水平,并增加了骨关节炎软骨中的净蛋白聚糖合成,尽管上述变化均无统计学意义。
双醋瑞因组与未治疗的骨关节炎对照组之间的差异,尽管无统计学意义,但表明双醋瑞因在这种快速进展的骨关节炎模型中具有活性。由于与骨关节炎起始相关的变化可能与进展相关的变化不同,因此应在进展较慢的模型中研究双醋瑞因是否具有改善病情的作用。