4周中等强度跑台运动对碘乙酸钠诱导的膝骨关节炎大鼠软骨病理特征及Cytl1-CCR2通路活性的影响

关键词：膝骨关节炎  跑台运动  细胞因子样蛋白1-CC 基序趋化因子受体2通路  软骨病理特征

Keywords:knee osteoarthritis  treadmill exercise  Cytl1-CCR2 pathway  pathological characteristics of cartilage

摘要：

      摘要 目的：探讨4周中等强度跑台运动对碘乙酸钠（monoiodoacetate， MIA）诱导的膝骨关节炎（knee osteoarthritis， KOA）大鼠软骨病理及细胞因子样蛋白1（cytokine-like 1， Cytl1）-CC基序趋化因子受体2（C-C motif chemokine receptor 2， CCR2）通路活性的影响。 方法：60只SD大鼠随机分为对照组、运动对照组、模型组和模型运动组。采用关节腔注射MIA诱导大鼠KOA模型，MIA注射后进行为期4周的中等强度跑台运动。动态记录大鼠体重和膝关节肿胀的变化，X线和体视显微镜观察大鼠膝关节骨赘、畸形等损伤表现，甲苯胺蓝染色评价大鼠膝关节软骨的结构变化，原位细胞死亡检测分析大鼠膝关节软骨细胞凋亡情况，基因表达综合数据库（gene expression omnibus，GEO）分析预测潜在的运动缓解KOA病理特征的关键通路，免疫组织化学染色或Western Blot检测大鼠膝关节软骨组织中相关分子的蛋白表达。 结果：成功建立大鼠KOA模型，4周中等强度跑台运动较好缓解KOA病理特征，抑制软骨退变和细胞凋亡；GEO数据库分析发现Cytl1-CCR2通路可能参与运动缓解KOA作用；4周中等强度跑台运动促进KOA大鼠软骨组织中Cytl1表达，抑制CCR2通路相关蛋白的表达。 结论：4周中等强度跑台改善KOA大鼠膝关节软骨损伤的病理特征，其作用可能与Cytl1-CCR2通路活性相关。

Abstract:

      Abstract Objective： To investigate the effects of 4-week moderate intensity treadmill exercise on knee cartilage pathology and the activity of Cytokine-like 1（Cytl1）-C-C motif chemokine receptor 2 （CCR2） pathway in knee cartilage of rats with monoiodoacetate（MIA） induced knee osteoarthritis （KOA）. Method： Sixty SD rats were randomly divided into control group， control and exercise group，knee osteoarthritis group and knee osteoarthritis and exercise group. The KOA model was induced by intraarticular injection of MIA， and the moderate intensity treadmill exercise was carried out for 4 weeks after MIA injection. The changes of body weight and knee joint swelling were recorded dynamically； the osteophytes and deformities of knee joint were observed by X-ray and stereomicroscope； the structural changes of knee cartilage were evaluated by toluidine blue staining； the apoptosis of chondrocytes was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling（TUNEL）；and the bioinformatics analysis of gene expression omnibus（GEO） data set was used to predict the potential key pathways of exercise alleviating KOA pathology. Immunohistochemical staining or Western Blot was used to detect the protein expression of related molecules in cartilage tissue. Result： The KOA rat model was successfully established， and 4-week moderate intensity treadmill exercise could alleviate the pathological characteristics of KOA and inhibit cartilage degeneration and apoptosis； bioinformatics analysis of GEO data set showed that Cytl1-CCR2 pathway might be involved in the alleviation of KOA by exercise； 4-week moderate intensity treadmill exercise promoted the expression of Cytl1， while inhibited the expression of proteins related to CCR2 pathway in cartilage tissue of KOA rats. Conclusion： 4-week moderate intensity treadmill can improve the pathological characteristics of knee cartilage injury in KOA rats， which might be related to the activity of Cytl1-CCR2 pathway.