IL-1β和MMP-13在兔骨关节炎模型软骨和滑液中的表达

摘要

Objective To investigate the feasibility of osteoarthritis (OA) model in rabbits by injuring medial meniscus so as to understand the role of interleukin-1 beta (IL-1β) and matrix metalloproteinase-13 (MMP-13) in pathological mechanism of articular cartilage and synovial fluid of OA model in rabbits.Methods We randomly divided 40 New Zealand white rabbits into experimental group (n =30) and control group (n =10).Pathological changes in articular cartilage of the femoral condyle were scored at weeks 2,6 and 12 after surgery.We detected the expressions of IL-1β and MMP-13 by immunohistochemistry.The cell fractions of IL-1β and MMP-13 were recorded by ELISA.Results The articular cartilage score and HE staining significantly differed at various time points of gross and pathological observation between control group and experimental group (P＜ 0.05).Immunohistochemistry showed that IL-1β was expressed in both groups and that the cell fraction differed significantly at weeks 6 and 12 (P＜0.05),but not at week 2 between the two groups.MMP-13 protein expression was not detected in articular condrocytes in control group,but was detected in experiment group with a significant difference (P＜0.05).IL-1β expression was consistent in articular cartilage and synovial fluid.Conclusion The reasonable rabbit animal OA model could be established by knee meniscus injury caused by surgical method.Expressions of IL-1β and MMP-13 change obviously in the pathomechanism of OA.Further clinical studies are needed to determine whether they can be used as markers in early diagnosis of OA.%目的 评价兔膝关节内侧半月板损伤制作骨关节炎(OA)模型的方法的可行性,探讨白细胞介素-1β(IL-1β)和金属蛋白酶-13(MMP-13)在兔骨关节炎模型软骨和滑液病变中的作用机制.方法 新西兰大白兔40只,随机分为实验组(n=30)和对照组(n=10),于术后2、6、12周观察股骨髁关节软骨的病理变化并进行评分;用免疫组化方法检测关节软骨中IL-1β和MMP-13的表达情况;用酶联免疫吸附法测定关节液中IL-1和MMP-13的含量.结果 实验组和对照组在大体和病理观察不同时间点关节软骨评分及HE染色差异均有统计学意义(P＜0.05).免疫组织化学检测结果显示IL-1β在两组中均有表达,实验组和对照组2周时细胞分数差异无统计学意义,6、12周差异有统计学意义(P＜0.05).MMP-13在对照组关节软骨细胞中未见表达,实验组的关节软骨细胞中可见MMP-13蛋白的表达,差异有统计学意义(P＜0.05).关节滑液中IL-1β表达和在软骨中表达一致.结论 采用损伤兔膝关节半月板的方法可建立合理的动物OA模型;IL-1β和MMP-13在OA发病过程中表达水平有明显变化,需要进一步的临床研究来探讨其是否可以作为早期诊断OA的指标之一.