不同干预因素对膝骨关节炎患者滑液中MMP-3和TIMP-1的影响  

Effect of various intervention factors on MMP-3 and TIMP-1 level in synovial fluid in knee joints with osteroarthritis

作　　者：徐海涛[1] 陈游[1] 陈立科[2] 李菊元[1] 张薇[1] 吴波[2] 

机构地区：[1]中南大学湘雅二医院骨科,长沙410011 [2]湖南省第二人民医院骨科,长沙410007

出　　处：《中南大学学报（医学版）》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)~~

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-3Objective 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 eff

关 键 词：膝关节 骨关节炎 基质金属蛋白酶-3 组织型基质金属蛋白酶抑制剂-1 

分 类 号：R684.3[医药卫生—骨科学]