C57黑鼠骨关节炎模型的关节病理积分与血清及滑膜中基质金属蛋白酶-3白细胞介素-1水平的相关性研究

目的 探讨基质金属蛋白酶(MMP)-3与白细胞介素(IL)-1在骨关节炎(OA)发病中所起的作用及其用于临床判断OA早期病理变化的可能性.方法 采用C57黑鼠OA模型.在自然增龄基础上,又对小鼠进行运动负荷训练.应用形态学方法对模型关节的病理切片观察,进行OA积分评分.研究采用酶联免疫吸附试验(ELISA)的方法.检测血清及滑膜中MMP-3、IL-1的水平.采用相关性分析来检验血清和滑膜中MMP-3、IL-1水平之间的关系,以及与OA积分评分之间的相关性.结果 ①形态学观察:C57黑鼠具有自发OA特征,其OA严重程度与周龄相关,且运动负荷可加快有自发OA倾向的小鼠关节软骨病理改变.②ELISA检测:运动负荷组滑膜中MMP-3[(84±6)ng/ml]、IL-1[(48±3)ng/ml]及血清中IL-1[(38.3±5.0 mg/ml]含量高于自然增龄组[滑膜MMP-3(71±5)ng,ml;IL-1(42±3)ng/ml;血清IL-1(8.1±2.4)ng/ml],差异有统计学意义(P<0.01);血清与滑膜中MMP-3、IL-1水平、OA评分存在线性相关[r均>0.67,P均<0.01].结论 联合检测MMP-3及IL-1在OA血清中的含量,有助于疾病的诊断与病情的判断.特别是MMP-3对于OA的早期诊断具有更为重要的意义.

Morphological studies on osteoarthritis of the articular cartilage in C57 black mice and its relationship with etalloproteinase-3 and lnterleukln-1 in serum and synovial fluid

Objective To study the levels of Matrix Metalloproteinase-3 (MMP-3) and interleukin (IL-1) in the synovial fluid and plasma of C57 black mice with osteoarthritis (OA) and their relationships with the severity of pathological changes so as to investigate their effects and correlation with OA. Methods The C57 black mice with OA were enrolled for this study. Different levels of exercise were appicated based on their age. Knee joint pathological changes were examined for pathological severity of OA. ELISA sandwich method was used to measure the levels of MMP-3 and IL-1 in serum and synovial fluid. Correlation analysis was performed to demonstrate the relationship between the levels of MMP-3 and IL-1 in the serum and synovial fluid, and the pathological severity of OA. Results ①Morphological observations: C57 black mice were characterized by spontaneously developing OA and the incidence and the severity of osteoarthritis gradually increased with age and exercising burdens. ② The level of MMP-3 and IL-1 in the synovial fluid of exercising mice MMP-3 (84±6) ng/ml, IL-1 (48±3) ng/ml was higher than that in the aged ones [MMP-3 (84±6) ng/ml, IL-1 (71±5) ng/ml J, the difference was significant (P<0.01). The level of MMP-3 and IL-1 level in the serum had a linear correlation with that of the synovial fluid. At the same time, they also had linear correlation with the pathological severity of OA (All r>0.67, and all P<0.01). Conclusion The levels of MMP-3 and IL-1 in serum and synovial fluid can help to make early diagnosis of OA, especially elevated MMP-3 level.