NT-3／TrkC信号通路在猴前交叉韧带本体感觉损伤中的作用

The changing of NT-3/TrkC proprioceptive signaling pathway after ACL injury

目的:探讨NT-3/TrkC信号通路在前交叉韧带(ACL)本体感觉损伤中的作用和机制。方法:选取12只正常的食蟹猴,随机选择9只食蟹猴进行关节镜下单侧ACL损伤造模后,将全部膝关节分为三组:正常组(3只正常食蟹猴每只选1个正常膝关节,共3个)、模型A组(9个模型中的健侧膝关节)和模型B组(9个模型中的损伤侧膝关节),模型A组和模型B组同属模型组。在造模后4、8、12周,运用RT-qPCR和Western Blot技术检测L2-S1DRG中NT-3、TrkC以及ACL中GAP-43基因和蛋白的表达水平。结果:在同一时间点,与正常组相比,模型组DRG中NT-3、TrkC的基因和蛋白相对表达量下降,有显著性差异(P<0.01)。与正常组相比,模型A组和模型B组ACL中GAP-43的基因和蛋白相对表达量上升,而模型B组又高于模型A组,有显著性差异(P<0.01)。在模型组不同时间点,DRG中NT-3、TrkC的基因和蛋白相对表达量随时间的增加而逐渐下降且均低于正常组,有显著性差异(P<0.01)。与正常组比较,在模型A组和模型B组不同时间点,ACL中GAP-43的基因和蛋白相对表达量均上升,但随时间的增加而逐渐下降,有显著性差异(P<0.01)。结论:NT-3/TrkC信号通路在ACL本体感觉损伤和康复中有着重要的作用。当ACL损伤时,引起局部GAP-43的表达上升,以及DRG中NT-3、TrkC的表达下降,同时对侧ACL本体感受器的功能也受到影响。

Objective： To investigate the changing and mechanism of NT-3/TrkC proprioceptive signaling pathway after ACL impairment. Method： Totally 12 normal cynomolgus monkeys were selected, and 9 among the 12 were randomly selected to being unilateral 1/4 ACL cut off under arthroscopy. The normal group included one knee of each non-operation monkeys,3 in total. A model group included contrast lateral knee joint in the 9 and B model group included the injured knee joint in the 9 RT-qPCR and Western-blot were used to detect the expression of GAP-43 gene and protein in L2-S1DRG, TrkC and ACL for normal monkeys and model groups at in 4, 8 and 12 weeks after modeling for for model groups.. Result： Comparing with normal group, the relative expression of NT-3 and TrkC in DRG decreased for model groups. The difference was significant （P〈0.01）. Comparing with the normal group, the relative expression of GAP-43 gene and protein in ACL increased in model groups, but the model group B was higher than the model group A （P〈0.01）. In the model groups at different time points, the relative expression of NT-3 and TrkC in DRG decreased gradually with the increase of time, and were lower than those in the normal group（P〈0.01）. Comparing with the normal group, the relative expression of GAP-43 gene and protein increased in ACL in the model A and model B groups at different time points,but it decreased with the time increased. Conclusion： NT-3/TrkC signaling pathway plays an important role in ACL rehabilitation. When ACL was injured, the expression of GAP-43 increased and NT-3 and TrkC decreased in the DRG, the changes also happened in contrast lateral ACL receptors.