关节腔内注射洛伐他汀预防骨关节炎软骨退变

The effects of lovastatin on matrix metalloproteinase-1 ,-3 mRNA expression in cartilage and synovium of osteoarthritis rabbits

目的研究洛伐他汀关节腔内注射对骨关节炎（OA）模型关节软骨退变及对基质金属蛋白酶（matrix metalloproteinase-1，3）mRNA表达的影响。方法30只6个月龄新西兰大白兔行右膝关节前交叉韧带切断术。手术后将动物随机分为实验组和对照组，实验组术后立即给予关节腔内注射0．5mg／ml洛伐他汀0．2ml／kg，每周1次，连续6周；对照组则关节腔内注射等容量的生理盐水。术后6周处死动物。在解剖镜下观察股骨内髁关节软骨的大体形态学改变并评分。用反转录一聚合酶链式反应检测软骨及滑膜中MMP-1，3mRNA的表达。结果解剖镜下实验组软骨退变程度较对照组明显减轻；实验组关节液中IL-1水平较对照组明显降低；实验组滑膜中MMP-1，3mRNA的表达水平显著低于对照组（P〈0．05），而软骨中的MMP-1，3mRNA的表达较对照组差异无统计学意义（P〉0．05）。结论在OA早期关节腔内注射L洛伐他汀能够明显降低MMP-1，3mRNA的表达，减轻骨关节炎软骨的退变。

Objective To observe the influence of intra-articular injection of lovastatin on cartilage degeneration and mRNA expression of matrix metalloproteinase-1 ,-3 （ MMP-1 ,- 3） in cartilage and synovium of osteoarthritis （OA） model. Methods Thirty New Zealand rabbits underwent unilateral anterior cruciate ligament transection （ACLT） were random divided into two groups. The rabbits in experimental group received 0.1 mg/ml intra-articular lovastatin injection at 0. 2 ml/kg of body weight immediately after surgery , once a week . Those in control group were treated with intra-articular injection of normal saline. At the 6th week after surgery, all rabbits were sacrificed. The articular cartilage degeneration of medial femoral condyle was evaluated under microscopy. Gene expression of MMP-1 ,-3 was detected by reverse transcription-polymerase chain reaction （RT-PCR） . Results Cartilage degeneration in untreated group was significantly more severe than that in experimental group. In cartilage, no significant difference on the expression of MMP-1 and MMP-3 mRNA was found between the experimental group and control group. In synovium, the expression of MMP-1 and MMP-3 mRNA was significantly suppressed in experimental group compared with control group. Conclusion During the development of experimental OA, intra-articnlar administration of lovastatin reduces the expression of matrix degrading enzyme, thus alleviate cartilage degradation.