运动训练对血清及关节液内软骨生物标记物水平的影响

目的了解软骨寡聚基质蛋白(COMP)、金属基质蛋白酶-1(MMP-1)、MMP-3、金属基质蛋白酶抑制因子-1(TIMP-1)作为生物标记物对不同运动训练模式下膝关节软骨早期运动性损伤及修复进行评估的意义。方法20只实验用狗随机分为一般训练组(训练组,n=8)、强化训练组(强化组,n=8)、对照组(n=4),训练组跑步路线坡度为10°,速度为200m/min;强化组跑步路线坡度为10°,速度为300m/min;对照组自由活动。于0、2、4、6、8、10周抽取3组动物血液及关节液,应用ELISA方法检测COMP、MMP-1、MMP-3、TIMP-1水平,并以MRI检查训练组及强化组动物膝关节软骨损伤情况。结果MRI检查显示训练组与强化组动物2周后均出现膝关节软骨运动性损伤改变,4~6周时最严重,6周后开始缓解。血清及关节液内COMP、MMP-1、MMP-3、TIMP-1浓度在训练开始后均有不同程度升高,并随时间改变而发生改变。血清COMP水平训练组与强化组分别于第4周和第6周达到最高,分别为5.7和6.8ng/ml;血清MMP-1水平训练组与强化组分别于第8周和第10周达到最高,分别为14.7和11.3ng/ml;血清MMP-3水平训练组与强化组都于第10周达到最高,分别为116.4和109.3ng/ml;血清MMP-3/TIMP-1水平训练组与强化组都于第10周达到最高,分别为0.365和0.410;关节液COMP水平训练组与强化组都于第4周达到最高,分别为14.2和17.9ng/ml;关节液MMP-1水平训练组与强化组都于第10周达到最高,分别为89.9和82.7ng/ml;关节液MMP-3水平训练组与强化组都于第6周达到最高,分别为6961.4和5832.1ng/ml;关节液MMP-3/TIMP-1水平训练组与强化组都于第6周达到最高,分别为8.434和7.243;血清及关节液内TIMP-1水平变化无明显规律。强化组MMP-1、MMP-3、MMP-3/TIMP-1总体水平低于训练组,COMP总体水平高于训练组,提示强化组关节损伤趋势低于训练组,修复程度高于训练组。血清与关节液中标记物浓度变化显著相关(P<0.01)。结论强化训练较一般训练能更好地促进关节软骨的塑形改建;联合应用数种生物标志物预测早期关节软骨损伤、修复情况及监测病程变化较影像学检查更为灵敏。

Effects of exercises on levels of cartilage biomarkers in serum and synovial fluid

Objective To explore the significance of such biological markers as cartilage oligomeric matrix protein (COMP), matrix metalloproteinases-1(MMP-1), matrix metalloproteinases-3 (MMP-3) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in serum and synovial fluid to evaluate early motional injury on knee joint cartilage induced by different modes of training. Methods Twenty adult dogs were randomly divided into three groups, i.e. common training group (n=8), short intensified training group (n=8) and control group (n=4). Magnetic resonance imaging (MRI) examinations were performed regularly (0, 2, 4, 6, 8, 10 weeks) to investigate the changes in the knee joint cartilage, while the concentrations of COMP, MMP-1, MMP-3 and TIMP-1 in serum and synovial fluid were measured by ELISA. Results It was revealed by MRI that the motional injury to knee joint cartilage occurred both in common training group and short intensified training group 2 weeks after training with different intensity, with severest injury occurring during 4~6 weeks after training, and then subsided gradually. The concentrations of COMP, MMP-1, MMP-3, TIMP-1 and MMP-3/TIMP-1 in serum and synovial fluid elevated in various degrees during training period with the lapse of time. Generally, the concentrations of MMP-1, MMP-3 and MMP-3/TIMP-1 in short intensified training group were lower, while that of COMP was higher, than that in common training group. The results suggested that the possibility of incurring articular injury in short intensified training group was lower than that in common training group, while the possibility of repairing the injury was on the contrary. Furthermore, the changes in levels of biomarkers in both serum and synovial fluid showed a close correlation. Conclusions Intensified training may result in moulding reconstruction better than the common training did. A combined determination of several biomarkers could be more sensitive than MRI examination on predicting the injury and repair of articular cartilage and on monitoring the course of illness. Therefore they are valuable for clinical application.