脱氢表雄酮对兔骨关节炎软骨和滑膜中MMP-3、TIMP-1和IL-1β mRNA表达的影响  

Effect of dehydroepiandrosterone on mRNA expression of MMP-3, TIMP-1 and IL-1β in the cartilage and synovium of rabbits with osteoarthritis

作　　者：余华晨[1] 吴立东[1] 熊炎[1] 冯洁[1] 

机构地区：[1]浙江大学医学院附属第二医院骨科,杭州310009

出　　处：《浙江医学》2006年第5期345-348,共4页Zhejiang Medical Journal

摘　　要：目的观察关节腔内注射脱氢表雄酮(DHEA)对兔骨关节炎软骨和滑膜中基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶组织抑制因子-1(TIMP-1)和白细胞介素-1β(IL-1β)mRNA表达的影响。方法20只新西兰大白兔行单侧前交叉韧带切除术,术后4周后分为实验组和对照组。实验组关节腔内注射100μmolLDHEA(溶于二甲基亚砜),每周1次,连续5周,对照组注射同剂量的二甲基亚砜。术后9周处死兔子,取膝关节行大体观察,用逆转录聚合酶链反应方法检测关节软骨和滑膜中MMP-3、TIMP-1和IL-1βmRNA的表达。结果大体观察显示实验组软骨和滑膜病变程度轻于对照组。实验组软骨和滑膜中MMP-3mRNA的表达水平显著低于对照组(均P<0.05),而TIMP-1mRNA的表达显著高于对照组(均P<0.05)。实验组软骨中IL-1βmRNA的表达与对照组的差异无统计学意义(P>0.05),而滑膜中IL-1βmRNA的表达显著低于对照组(P<0.01)。结论DHEA能有效延缓兔骨关节炎的进展。下调软骨、滑膜中MMP-3和上调软骨、滑膜中TIMP-1的表达及下调滑膜中IL-1β的表达可能是DHEA对骨关节炎的作用机制。Objective To observe the effects of intra-articular injection of dehydroepiandrosterone （DHEA） on mRNA expression of metalloproteinases-3 （MMP-3）,tissue inhibitor of metalloproteinases-1 （TIMP-1） and interleukin-lbeta （ IL-1β ） in the cartilage and synovium of rabbits with osteoarthritis. Methods Twenty New Zealand rabbits underwent unilateral anterior cruciate ligament resection and were divided into two groups. The animals in experimental group were injected in the knees with 100 μmol/L DHEA in dimethylsulphoxide 4 weeks after resection, once a week for five weeks. Rabbits in the control group were treated under the same condition using dimcthylsulphoxide. All rabbits were sacrificed 9 weeks after operation and the knee joints were examined by gross morphology. The mRNA expression of MMP-3, TIMP-1 and IL-1β in the cartilage and synovium was analyzed using reverse transcription polymerase chain reaction. Results Gross morphologic inspec- tion showed that the extent of cartilage and synovium danlage in the experimental group were less severe than in the control group. The expression of MMP-3 mRNA in cartilage and synovium was significantly decreased （both P〈0.05）, while the expression of TIMP-1 mRNA was significantly increased in the experimental group compared with that in the control group （both P〈0.05）. No significant difference of IL-1β mRNA expression in the cartilage was found between the experimental and control group （P〉0.05）, however it was significantly suppressed in experimental group compared with control group（P〈0.01）. Conclusion DHEA can inhibit the progression of osteoarthritis in the experimental model. Down-regulation of MMP-3 and up-regulation of TIMP-1 in cartilage and synovium and down-regulation of IL-1β in the synovium may be the mechanism of protective effect of DHEA on osteoarthritis.

关 键 词：脱氢表雄酮 骨关节炎 基质金属蛋白酶 基质金属蛋白酶组织抑制因子 白细胞介素-1Β 

分 类 号：R684.3[医药卫生—骨科学]