运动致软骨损伤发生过程中TGF-β/ALK/Smad信号通路的表达变化

TGF-β/ ALK / Smad Signaling Pathways in Exercise-induced Articular Cartilage Injury

目的探讨不同强度跳跃运动诱发关节软骨损伤过程中,软骨组织中TGF-β/ALK/Smad信号通路的相对表达情况。方法将SD大鼠随机分为3组,其中低强度运动组和高强度运动组均在自制电刺激装置内进行跳跃运动训练,运动时间均为每天40 min,中间休息10 min,每周训练6 d,休息1 d,连续进行3周。其中高强度运动组大鼠运动训练时,自制装置中每10 s通电一次;低强度运动组每30 s通电一次;对照组大鼠进行自由活动。在分组干预的第1周、2周、3周分别处死5只大鼠,观察左后肢膝关节软骨表面形态,取部分软骨组织利用qRT-PCR法测定ALK5、ALK1、Serpine1、Id1和GAPDH基因的mRNA表达水平。结果随着运动训练强度的加大和时间的延长,大鼠膝关节软骨表面损伤情况逐渐加重;与对照组同期相比,在运动相关软骨损伤早期,大鼠膝关节软骨中TGF-β/ALK5/Smad2/3信号通路代偿性活化,而至第3周末,该通路活化水平却明显低于对照组;与之相反,在软骨损伤发生过程中,TGF-β/ALK1/Smad1/5/8信号通路活化水平持续高于对照组,其中以高强度运动组活化更为明显。结论转化生长因子β1下游两个主要信号通路(ALK5/Smad2/3与ALK1/Smad1/5/8)的相对活化水平失衡介导的软骨细胞分化状态异常可能是运动相关性软骨损伤的发生机制之一。

O bjective To explore the role of TGF-β / ALK / Smad signaling pathways in articular cartilage injury induced by jumping exercises of different intensities. M ethods SD rats were randomly divided into 3 groups,including low intensity exercise group and high intensity exercise group,which underwent the jumping exercises for 40 min / d,6 d / w for 3 week in an autonomous electrical stimulation equipment. The frequency of electrical stimulation was set up to every 10 s for low intensity exercise group and every 30 s for high intensity exercise group. In the end of 1week,2week and 3week,5 rats of every group were put to death and the left hind leg knee joint cartilage were used to determine the relative mRNA expression levels ALK5,ALK1,Serpine1,Id1 and GAPDH gene with qRT-PCR. R esults Increased with the strength and duration of the exercises,the rat knee joint cartilage surface injury gradually aggravated. Compared with the control group in the same time point,TGF-β / ALK5 / Smad2 /3 signaling pathway was activated for compensatein the early stage of knee joint cartilage injury,and was significantly suppressed by the end of the third weeks. By contrast,TGF-β / ALK1 / Smad1 /5 /8 signaling pathway was always activated during the knee joint cartilage injury,especially in the high intensity exercise group. C onclusion The imbalance of two main downstream signaling pathways of transforming growth factor beta 1（ ALK5 / Smad2 /3 and ALK1 / Smad1 /5 /8） mediatesthe abnormal state of chondrocyte differentiation,which may beinvolved in exercise-induced cartilage injury.