透明质酸钠对兔骨关节炎软骨和滑膜中MMP-1-3及其组织抑制物mRNA表达的影响

The effects of sodium hyaluronate on matrix metalloproteinase-1, -3 and tissue inhibitor of metalloproteinase-1 mRNA expression in cartilage and synovium of osteoarthritis rabbits

目的观察透明质酸钠(HA)关节腔注射对骨关节炎(OA)模型关节软骨及滑膜中的基质金属蛋白酶(MMP)-1、MMP-3及其组织抑制物(TIMP)-1mRNA表达水平的影响。方法16只大耳白兔行单侧前交叉韧带切断术,术后5周将动物随机分为实验组和对照组,实验组关节腔注射1%HA0.3ml,每周1次,连续5周,对照组则注射等量生理盐水。术后10周观察两组动物股骨内髁关节软骨光镜下的病理改变,采用反转录-聚合酶链反应(RT-PCR)方法检测关节软骨及滑膜中MMP-1、MMP-3及TIMP-1mRNA的表达。结果实验组软骨退变程度较对照组明显减轻,实验组滑膜中MMP-3的mRNA表达水平显著低于对照组(0.40±0.10vs0.62±0.13),而软骨中的MMP-3的表达较对照组差异无显著性,MMP-1和TIMP-1在实验组和对照组软骨及滑膜中的mRNA表达差异无显著性。结论HA能有效地减轻早期OA关节软骨的退变,其对早期OA的治疗作用的机制之一可能是抑制滑膜MMP-3的表达。

Objective To observe the influence of intra-articular injection of sodium hyaluronate (HA) on mRNA expression of matrix metalloproteinase (MMP) -1, -3 and tissue inhibitor of metalloproteinase (TIMP)-1 in cartilage and synovium of osteoarthritis (OA) . Methods Sixteen white rabbits underwent unilateral anterior cruciate ligament transection and were divided into 2 groups randomly 5 weeks after transection. Experimental group rabbits received 0.3 ml of intra-articular 1% HA injection once a week. Animals in control group were treated under the same condition using saline. At death, 10 weeks following surgery, histological changes of articular cartilage of medial femoral condyle were evaluated by microscopy. The mRNA expression of MMP-1, MMP-3 and TIMP-1 in cartilage and synovium was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) . Results Cartilage degradation in experimental group was significantly less severe than that in the control group. The expression of MMP-3 mRNA in synovium was significantly suppressed in experimental group compared with the control group (0.40±0.10 vs 0.62±0.13). HA treatment had no effect on MMP-3 expression in cartilage. No significant difference of MMP-1 and TIMP-1 expression in cartilage and synovium was found between experimental group and control group. Conclusion HA can alleviate the degeneration of articular cartilage of OA. One possible mechanism of the therapeutic effect of HA may be inhibition of expression of MMP-3 in synovium during early stage of OA.