骨关节炎兔血清中软骨寡聚基质蛋白和基质金属蛋白酶-3水平

A study of serum cartilage oligomeric matrixprotein and matrix metalloproteinase-3 concentration in osteoarthritic rabbit models

目的 探讨血清软骨寡聚基质蛋白（COMP）与基质金属蛋白酶（MMP）-3检测应用于临床评估骨关节炎（OA）软骨病理改变的可能性.方法 伸直位石膏管型制动16只兔右后膝关节制作OA模型.以造模时间不同分为造模2周、造模6周,左后膝关节未造模故为对照组.X线影像学与病理观察模型关节的变化;评估关节软骨降解程度（OA积分）;ELISA检测兔血清COMP、MMP-3水平;分析血清COMP、MMP-3水平与OA积分间的相关性.结果 （1）造模2周影像学变化较造模前不明显;造模6周兔胫骨平台边缘不光滑,关节间隙变窄,表面有毛刺样增生,胫骨平台及股骨内髁外侧可见唇样增生.（2）OA关节病变的形态学观察：造模2周兔关节软骨表面粗糙,表层裂隙;软骨细胞弥漫增多,排列紊乱;OA积分为（4.000±2.204）分.造模6周兔关节软骨表层可见较多裂隙延伸向下深达辐射层;裂隙周围可见脱水固缩坏死的软骨细胞且排列紊乱,部分成簇增生,各层结构不易分辨,有血管翳通过;OA积分为（10.620±1.408）分,与造模2周比,P=0.000.（3）造模2周兔血清COMP[（3.64±0.18）μg/L]、MMP-3[（1.99±0.81）μg/L]水平高于造模前[COMP（3.35±0.20）μg/L,MMP-3（1.61±0.71）μg/L];造模6周兔血清COMP[（3.96±0.44）μg/L]、MMP-3[（3.44±0.91）μg/L]水平高于造模前和造模2周,差异有统计学意义（P值均＜0.05）.血清COMP、MMP-3水平与OA积分呈线性相关关系（r值均＞0.710,P值均小于0.05）.结论 OA血清中COMP和MMP-3水平对评估OA软骨降解程度具有重要意义.

Objectiye To study the levels of cartilage oligomeric matrixprotein （COMP） and matrix metalloproteinase-3 （MMP-3） in the serum fluid of osteoarthritic rabbit models and their relationships with the severity of pathological changes, so as to investigate their correlation with osteoarthritis（OA）. Methods The osteoarthritic animal models were get from immobilizing the right knees of 18 rabbits in full extension using plaster cast. Knee joint pathological changes of 2,6 weeks were examined for pathological severity of OA; ELISA sandwich method was used to measure the levels of COMP and MMP-3 in serum before and after modeling（ at 2, 6 weeks respectively）; X ray of model keens was also obtained in different period.Correlation analysis was performed to demonstrate the relationship between the levels of COMP, MMP-3 in the serum and the pathological severity of OA. Results （ 1 ） Morphological observations： immobilizing the right knees of rabbits in full extension using plaster cast was a reliable methed for osteoarthritic animal models and the typical histopathologic character was seen; the severity of osteoarthritisgradually increased with time extended. （2） The levels of COMP[（3.64 ±0. 18）μg/L], MMP-3 [（1.99 ±0. 81 ） μg/L]in the serum of 2 weeks osteoarthritic animal models were higher than those before immobilizing with plaster cast [COMP（3.35 ±0. 20） μg/L,MMP-3（ 1.61 ±0. 71 ） μg/L]. The levels of COMP[（3.96 ±0. 44） μg/L],MMP-3[（3.44 ±0. 91） μg/L] of 6 weeks were much higher,with a significant difference（P 〈0.05）. The levels of COMP, MMP-3 in serum had a linear correlation with the pathological severity of OA （r 〉0. 710,and P 〈 0. 05 ）. Conclusion The levels of COMP and MMP-3 in serum can help to predict and evaluate the progression of OA.