Akasaki Y, Matsuda S, Nakayama K, Fukagawa S, Miura H, Iwamoto Y
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Osteoarthritis Cartilage. 2009 Feb;17(2):235-43. doi: 10.1016/j.joca.2008.06.012. Epub 2008 Jul 30.
To examine the therapeutic efficacy of an HMG-CoA reductase inhibitor (statin) in rabbit osteoarthritis (OA) in vitro and in vivo.
In the presence or absence of mevastatin, rabbit chondrocytes and synoviocytes were incubated with Interleukin-1beta (IL-1beta), and analyzed by biochemical methods. Thirty-two mature rabbits that underwent bilateral anterior cruciate ligament transaction (ACLT) received six consecutive weekly intra-articular injections of mevastatin at three different concentrations or a control solution. All animals were sacrificed 6 weeks after ACLT, and the knee joints were assessed by morphological, histological, immunohistochemical, and biochemical methods.
Mevastatin inhibited IL-1beta stimulation of gene expression of monocyte chemoattractant protein-1 (MCP-1) and matrix-metalloproteinases 3 (MMP-3), in synoviocytes but not chondrocytes. The levels of MCP-1 and MMP-3 productions in synoviocytes were significantly reduced by statin-treatment. In rabbit with OA, intra-articular injection of mevastatin significantly reduced cartilage degradation, as assessed by morphological and histological examinations. Synovial tissues of knees treated with mevastatin showed less severe inflammatory responses with reduced thickness of synovial cell lining and less infiltration of subsynovial CD68+monocyte lineage cells compared to untreated control knees. Relative mRNA expressions of MCP-1, IL-1beta, MMP-3, and MMP-13 were reduced in synovial tissues, but not articular cartilage, of knees treated with mevastatin compared with untreated control knees.
During the development of experimental OA, intra-articular administration of HMG-CoA reductase inhibitor (statin) reduces inflammatory cell infiltration and matrix-degrading enzyme expression, thus limiting cartilage degradation.
研究HMG-CoA还原酶抑制剂（他汀类药物）对兔骨关节炎（OA）的体内外治疗效果。
在有或没有美伐他汀存在的情况下，将兔软骨细胞和滑膜细胞与白细胞介素-1β（IL-1β）共同孵育，并用生化方法进行分析。32只成熟兔接受双侧前交叉韧带切断术（ACLT），连续6周每周关节内注射三种不同浓度的美伐他汀或对照溶液。所有动物在ACLT后6周处死，通过形态学、组织学、免疫组织化学和生化方法对膝关节进行评估。
美伐他汀抑制IL-1β对滑膜细胞而非软骨细胞中单核细胞趋化蛋白-1（MCP-1）和基质金属蛋白酶3（MMP-3）基因表达的刺激。他汀类药物治疗显著降低了滑膜细胞中MCP-1和MMP-3的产生水平。在患OA的兔中，通过形态学和组织学检查评估，关节内注射美伐他汀可显著减少软骨降解。与未治疗的对照膝关节相比，用美伐他汀治疗的膝关节滑膜组织炎症反应较轻，滑膜细胞衬里厚度减小，滑膜下CD68+单核细胞系细胞浸润较少。与未治疗的对照膝关节相比，用美伐他汀治疗的膝关节滑膜组织中MCP-1、IL-1β、MMP-3和MMP-13的相对mRNA表达降低，但关节软骨中未降低。
在实验性OA的发展过程中，关节内给予HMG-CoA还原酶抑制剂（他汀类药物）可减少炎症细胞浸润和基质降解酶表达，从而限制软骨降解。
