摘要
目的:观察透明质酸钠(hyaluronic acid,HA)、硫酸氨基葡萄糖(glucosamine sulfate,GS)、关节镜下关节清理术(arthroscopic debridment,AD)治疗膝骨关节炎(osteoarthritis,OA)时,对关节液内基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)、组织型金属蛋白酶抑制剂-1(tissue inhibitor of metallo-proteinase-1,TIMP-1)水平的影响,并探讨其治疗OA的机制。方法:60例膝OA病人(64关节)分为HA组和GS+HA组,并于HA组和GS+HA组选取部分病例组成HA′组和GS+HA′组,再与AD组比较。于治疗前和治疗后4周、6月抽取关节液样本,采用双抗体夹心ELISA法测定关节液内MMP-3和TIMP-1水平。结果:HA组和GS+HA组治疗4周时关节液中MMP-3水平及MMP-3/TIMP-1比值均较治疗前降低(P<0.01),且在治疗半年后MMP-3水平和MMP-3/TIMP-1比值下降仍有统计学意义(P<0.01)。GS+HA组治疗4周时TIMP-1水平较治疗前显著升高(P<0.01);HA组治疗4周时TIMP-1水平虽较治疗前升高,但无统计学意义(P>0.05)。AD组治疗4周与治疗前比较,关节液中MMP-3水平降低(P<0.01),TIMP-1水平升高(P<0.01),MMP-3/TIMP-1比值降低(P<0.01);且在治疗半年后MMP-3水平、MMP-3/TIMP-1比值下降仍有统计学意义(P<0.01);但治疗6月后与治疗4周比较,TIMP-1水平降低(P<0.01),MMP-3/TIMP-1比值升高(P<0.01)。HA组与GS+HA组比较,GS+HA组治疗4周时TIMP-1升高水平显著高于HA组(P<0.01)。AD组与相应的HA′组、GS+HA′组比较,治疗4周时AD组的TIMP-1升高最明显(P<0.01),其余指标无明显差异。结论:⑴HA,GS和AD治疗均能使膝关节OA患者关节液内的MMP-3水平、MMP-3/TIMP-1比值降低。⑵HA对关节液内的TIMP-1水平无明显影响,但同时应用GS可使关节液内的TIMP-1水平升高。HA和GS可通过不同的机制发挥治疗OA的作用。HA联合GS治疗可能获得更好的疗效。⑶在中、重度膝关节OA患者中,与相应的HA′组、GS+HA′组比较,治疗4周后AD组TIMP-1升高最明显,AD可能获得更好的疗效。⑷对MMP-3和TIMP-1的影响,可能是HA,GS和AD改善OA病情的重要机制。
Objective To examine the expression of MMP-3 and TIMP-1 in the synovial fluid in knee joints with osteoarthritis before and after being treated with hyaluronic acid （HA）, glucosamine sulfate （GS） and arthroscopic de bridment （AD） , and to explore the therapeutic mechanism. Methods Sixty patients （64 knees ） with osteoarthritis（ OA ） were randomly divided into HA group AD group and GS ＋ AD group. Some patients from the HA group and the GS ＋ HA group were selected, and served as HA′ group and GS ＋ HA′ group. The expression of MMP-3 and TIMP-1 in the synovial fluid was measured by enzyme-linked immunosorbent assay （ ELISA ） before and after 4 week and 6 month therapy. Results The level of MMP-3 and the ratio of MMP-3/TIMP-1 in the synovial fluid decreased after being treated for 4 weeks, and the effect on MMP-3 and MMP-3/ TIMP-1 lasted for 6 months in the HA group and the GS ＋ HA groups. The levels of TIMP-1 increased significantly after being treated for 4 weeks only in the GS ＋ HA group. The level of MMP-3 and the ratio of MMP-3/TIMP-1 in the synovial fluid decreased, but the level of TIMP-1 increased after being treated for 4 weeks, and the effect on MMP-3 and MMP-3/TIMP-1 lasted for 6 months. The level of MMP-3 and the ratio of MMP-3/TIMP-1 in the synovial fluid increased after being treated for 6 months compared with those for 4 weeks. The level of TIMP-1 increased in the GS group more than that in the HA group after being treated for 4 weeks. The level of TIMP-1 increased in the AD group more than that in the HA′ group and the GS ＋ HA′ group after being treated for 4 weeks. Conclusion （1） HA, GS and AD all can decrease the level of of MMP-3 and the ratio of MMP-3/ TIMP-1 in the synovial fluid in knee joints with OA. （2） The level of TIMP-1 in the synovial fluid has no difference before and after being treated with HA. The AD group and GS group can increase the level of TIMP-1 , which indicates that the AD group or GS group might produce better therapeutic effect. （3） The level of TIMP-1 increased in the AD group is more than that in the HA′ group and the GS ＋ HA′ group after being treated for 4 weeks, which indicates that the AD grorp might get better therapeutic effect than the other 2 groups. （4） One of the most important mechanisms of HA, GS and AD in treating OA might be attributed to the expression of MMPs and TIMPs in knee joints with OA.
出处
《中南大学学报（医学版）》
CAS
CSCD
北大核心
2008年第1期47-52,共6页
Journal of Central South University ：Medical Science
基金
湖南省卫生厅资助项目(B2003-058)~~
