胶原关节炎大鼠滑膜组织核转录因子κB与白细胞介素1β和基质金属蛋白酶9相关性分析

目的 探讨白细胞介素1β(IL-1β)、基质金属蛋白酶9(MMP-9)、核因子κB(NF-κB)与类风湿关节炎发生发展的相关性.方法 构建Ⅱ型胶原诱导的胶原关节炎大鼠模型,分不同时点处死动物,检测滑膜细胞中IL-1β,NF-κB和MMP-9的表达,分析大鼠关节炎评分与滑膜细胞NF-κB、IL-1β、MMP-9的表达的相关性.结果 实验组造模前关节体积为(2.18±0.16)ml,造模后2、4、6周分别为(4.68±0.49)、(5.62±0.59)、(5.44±0.66)ml,与造模前比较,差异均有统计学意义(P＜0.01);对照组造模前和造模后2、4、6周关节体积分别为(2.15±0.26)、(2.38±0.32)、(2.19±0.31)、(2.18±0.26)ml.造模后2、4、6周实验组大鼠关节体积与对照组比较,差异有统计学意义(P＜0.01).实验组大鼠造模后2、4、6周关节指数分别为(8.00±0.32)、(9.80±0.66)、(9.40±0.51),与对照组(均为0)比较,差异有统计学意义(P＜0.05).大鼠关节指数与NF-κBp65呈显著正相关(r=0.593,P＜0.05);MMP-9与NF-κBp65呈显著负相关(r=-0.506,P＜0.05).结论 实验组大鼠滑膜组织中NF-κB与IL-1β表达水平显著高于正常对照滑膜组织,且与关节炎的评分有一定相关性;提示NF-κB在类风湿关节炎发病机制中起关键的调控作用.

Abstract：

Objective To investigate the corelation among interleukins-1β (IL-1β), matrix metalloproteinase 9 ( MMP-9), nuclear factor kappa B (NF-κB) and arthritis index (AI) in the development of arthritis, and to understand the pathology of synoviocyte. Methods Thirty-six female Wistar rats were randomly divided into two groups,namely the model controlled group and the normal controlled group; three subgroups were randomly divided into model group and controlled group. The model group rats were immunized with emuusified bovine type Ⅱ collagen in complete Freund'adjuvant by introdemal injection to induce collagen induced arthritis (CIA) on day1, day14 and day 28, while the controlled group were injected with saline at the same time. The model and the controlrats were killed at different times. We detected the expression and activation levels of IL-1β, MMP-9 and NF-κB in synovial tissue by immunohistochemistry. Then we analyzed the corelation between AI and the expression of IL-1 β, MMP-9 and NF-κB in the synovium and IL-6 and TNF-α in the serum. Results The joint volume of model group was (2. 18 ± 0. 16), (4.68 ± 0.49 ), (5.62 ± 0. 59), (5.44 ± 0.66 ) respectively before, 2, 4 and 6 weeks after setting up models. There were statistically significant differences between before and after setting up models ( P ＜ 0. 01 ).The joint volume of control group was ( 2. 15 ± 0.26), (2.38 ± 0.32), (2. 19 ± 0. 31 ), ( 2.18 ± 0.26 ) respectively before, 2, 4 and 6 weeks after making model. Through measuring joints sizes after successfully modeling 2, 4 and 6 weeks, there were statistically significant differences between model and control group( P ＜0.01 ). MMP-9 showed significant negative correlation with NF-κB P 65 ( r = -0. 506, P ＜ 0.05 ). Conclusions The expression levels of IL-1 β and NF-κB are significantly higher in CIA synovial than those in control group and show a positive correlation with AI. NF-κB plays acritical role in the pathology of RA via regulating inflammation reaction, facililating the prolifteration of synoviocyte and participating the reestablishment of articulation.