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中华神经创伤外科电子杂志 ›› 2015, Vol. 01 ›› Issue (02) : 31 -35. doi: 10.3877/cma.j.issn.2095-9141.2015.02.010

基础研究

激活低密度脂蛋白受体相关蛋白-1依赖的细胞信号通路可促进轴突生长及神经损伤修复
李超1, 欧阳佳2, 朱军1,()   
  1. 1.063009 唐山,华北理工大学医学院
    2.330031,南昌大学基础医学院
  • 收稿日期:2015-03-13 出版日期:2015-04-15
  • 通信作者: 朱军

The activation of low density lipoprotein receptor related protein-1 dependent cell signaling pathway promotes axon growth and repair of nerve injury

Chao Li1, Yangjia Ou2, Jun Zhu1,()   

  1. 1.North China University of Science and Technology, Tangshan 063009, China
    2.Faculty of Basic Medical Science Nanchang University,Nanchang 330031,China
  • Received:2015-03-13 Published:2015-04-15
  • Corresponding author: Jun Zhu
引用本文:

李超, 欧阳佳, 朱军. 激活低密度脂蛋白受体相关蛋白-1依赖的细胞信号通路可促进轴突生长及神经损伤修复[J]. 中华神经创伤外科电子杂志, 2015, 01(02): 31-35.

Chao Li, Yangjia Ou, Jun Zhu. The activation of low density lipoprotein receptor related protein-1 dependent cell signaling pathway promotes axon growth and repair of nerve injury[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2015, 01(02): 31-35.

目的

初步探讨低密度脂蛋白受体相关蛋白-1(LRP1)依赖的信号通路对轴突生长及神经损伤修复的作用。

方法

在培养胎鼠皮层神经元过程中加入LRP1激动剂RBD,观察其与对照组相比能否促进神经突触的生长及其信号机制,此外通过制作小鼠脊髓损伤模型并予以鞘内注射RBD,观察其对神经损伤修复的影响。

结果

体外培养皮层神经元中加入RBD 后引起神经营养因子受体TrkC,Akt信号转导通路和细胞外调节蛋白激酶(ERK)的活化,其与对照组相比定量分析表达均明显升高(P<0.05),促进神经突的生长。鞘内注射RBD后小鼠脊髓损伤后的运动功能恢复评分也明显提高(P<0.05)。

结论

激活LRP1依赖的信号通路可明显促进轴突生长及小鼠脊髓损伤后的功能修复。

Objective

To investigate the effects of the low density lipoprotein receptors-1(LRP1) dependent signal pathway in axonal growth and nerve regeneration after injury.

Methods

Adding RBD, LRP1 agonist, when culture the cortical neurons of fetal rats, observing whether it can promote the growth of synapses and what the signal mechanism it is compared with the control group.In addition,observing the effects of RBD on the repair of nerve injury through building the spinal cord injury model of rats up and intrathecal inject the RBD.

Results

The activation of neurotrophic factor receptor TrkC,Akt signal transduction pathway and extracellular regulated protein kinase(ERK)which were induced after add RBD in cortical neuron in vitro. The results of quantitative analysis of expression between the intervention group and the control group were significantly increased(P<0.05), the growth of neurite were promoted. The recovery of motor function after spinal cord injury scores were significantly improved after the intrathecal injection of RBD in mice.

Conclusion

The activation of signal pathway dependented by LRP1 can obviously promote the growth of axon and repair functions of rats after the spinal injury.

图1 LRP-1在对照组、RBD、RAP与RBD+RAP组小鼠的活化程度 A-C:在成年小鼠未损伤脊髓中免疫荧光双标LRP-1(绿)和NF200(红),显示LRP-1和NF200共定位(×500)。D:培养18 h后对各组最长神经突触进行统计分析,经LSD-t检验显示,与对照组相比RBD明显促进神经突触的生长(P<0.01)。
图2 不同组间采用immunoblot检测的表达 A:vehicle、RBD (200 nmol/L)刺激体外培养神经元30 min 后通过immunoblot 检测pTrkC 的表达。B:体外培养神经元经vehicle 和k252A(10 nmol/L)预处理后使用RBD处理30 min,通过immunoblot检测pERK的表达。
图3 RBD组与对照组小鼠的旷场实验结果 A:旷场实验结果显示鞘内注射RBD 后,运动功能恢复明显高于对照组;B:经旷场实验检测其功能恢复至BMS Score>5的方可进行步态分析,步态检测显示RBD 组错步数量明显少于未处理组(*P<0.05)
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