Wnt5a修饰的神经干细胞通过MAPK/JNK和RhoA/Rock信号通路Cross-talk促进脊髓损伤修复的作用机制研究

神经干细胞(NSC)移植一直是治疗脊髓损伤的研究热点之一。然而，NSC移植治疗仍然面临着移植到体内后其神经元分化率低下的困境。因此，提高NSC向神经元的定向分化率，对脊髓损伤的修复具有关键作用。既往研究指出MAPK/JNK是经典的促进NSC向神经元分化的信号通路；同时RhoA/Rock是抑制NSC向神经元分化的信号通路。我们的预实验结果发现Wnt5a具有激活MAPK/JNK信号通路并抑制RhoA/Rock信号通路的双重作用。提示过表达Wnt5a的NSC将能更好地向神经元分化。由此我们提出科学假设：Wnt5a过表达的神经干细胞激活MAPK/JNK从而促进NSC向神经元定向分化；同时抵抗RhoA/Rock信号通路的抑制神经元分化的作用，最终能够高效率地向神经元分化，理想地重建神经回路，修复脊髓损伤和恢复神经功能。本课题采用一系列体内外实验证明该假设，为脊髓损伤的治疗提供新靶点和思路。

Neural stem cell (NSC) transplantation has been a most current topics in the treatment of spinal cord injury (SCI). However, the most formidable problem is, the neuronal differentiation rate of NSC is quite limited. Therefore, it plays a key role to induce the neuronal differentiation of NSC and improve the differentiation rate of NSC in the repair of spinal cord injury. Previous studies have shown that Wnt5a can activate MAPK/JNK pathway to promote neuronal differentiation and reduce RhoA expression so as to inhibit the activation of RhoA/Rock signaling pathway. Thus, we hypothesize that Wnt5a-overexpressed NSC transplanted into spinal cord after injury, Wnt5a up-regulated MAPK/JNK signal pathway and inhibited the activation of RhoA/Rock signal pathways to promote the neuronal differentiation of NSC and improve motor function of spinal cord injury. To prove this hypothesis, we propose the current study, including in vitro study for investigating the molecular mechanism of Wnt5a-NSC promote neuronal differentiation in NSC through MAPK/JNK and RhoA/Rock cross-talk, as well in vivo study for validating its role in SCI. The potential findings would provide more insight of SCI and help with identification of novel treatment strategy.