Yan Zhao-wei, Dong Ji, Qin Chen-hao, Zhao Chun-yang, Miao Li-yan, He Chun-yan
Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
Mediators Inflamm. 2015;2015:780149. doi: 10.1155/2015/780149. Epub 2015 Oct 11.
Osteoarthritis (OA) is a slowly progressive joint disease typically seen in middle-age to elderly people. At present, there is no ideal agent to treat OA. Chenodeoxycholic acid (CDCA) was a principal active constituent from animal bile. However, the therapeutic effect of CDCA on OA severity was largely unknown. The purpose of this study was to evaluate the therapeutic effect of intra-articular injection of CDCA in a rabbit OA model. OA was induced in experimental rabbits by anterior cruciate ligament transection (ACLT) and then rabbits were intra-articularly injected with CDCA (10 mg/kg or 50 mg/kg) once per week for 5 weeks. The results showed that CDCA significantly decreased cartilage degradation on the surface of femoral condyles, reducing the pathological changes of articular cartilage and synovial membrane by macroscopic and histological analysis. CDCA also significantly decreased bone destruction and erosion of joint evaluated by micro-CT. Furthermore, CDCA could markedly reduce the release of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), interleukin-1β (IL-1β), and prostaglandin E2 (PGE2) in synovial fluid. These observations highlight CDCA might be a potential therapeutic agent for OA.
骨关节炎(OA)是一种常见于中老年人的缓慢进展性关节疾病。目前,尚无理想的治疗OA的药物。鹅去氧胆酸(CDCA)是动物胆汁中的主要活性成分。然而,CDCA对OA严重程度的治疗效果尚不清楚。本研究旨在评估关节腔内注射CDCA对兔OA模型的治疗效果。通过前交叉韧带横断术(ACLT)诱导实验兔发生OA,然后每周一次关节腔内注射CDCA(10mg/kg或50mg/kg),持续5周。结果显示,通过宏观和组织学分析,CDCA显著减少了股骨髁表面的软骨降解,减轻了关节软骨和滑膜的病理变化。通过显微CT评估,CDCA还显著减少了关节的骨质破坏和侵蚀。此外,CDCA可显著降低滑液中基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶-3(MMP-3)、白细胞介素-1β(IL-1β)和前列腺素E2(PGE2)的释放。这些观察结果表明,CDCA可能是一种潜在的OA治疗药物。