从Slit/Robo-Rho/Rho激酶信号通路研究电针促进周围神经损伤轴突靶向再生修复机制

Peripheral nerve injury（PNI）regeneration is one of the hottest discussed problems in modern medicine field. Although electroacupuncture (EA) treatment of PNI has been showed with certain advantages, but its mechanism still needs further investigation. In our former research we noticed this key factor that was axonal targeting regeneration. We have already found that EA of PNI could increase the axon guidence factors Slit1/2 and their mRNA expression level, and Slit/Robo signal pathway mediated by srGAP crosslinked with Rho/Rho kinase signal pathway. Therefore, we conjecture EA treatment of PNI may have the relation with them. Base on this hypothesis, guided by the acupuncture and moxibustion theory of traditional Chinese medicine, we copy the PNI model in rats, on the whole, tissue, cellular and molecular level, through nerve tracing with Nuero-Dil in vivo,immunofluorescence, electron microscopy, RT-PCR, Western Blot and other techniques, and application of signaling inhibitors Robo-Fc, Y-27632 to block for comparative observation respectively, dynamically to observe the influence law of EA at Huantiao and Zusanli acupoints in PNI rats to related key molecules at all levels:Slit,Robo, srGAP, Cdc42,Rac1, RhoA, to study the connection between EA treatment of PIN and the Slit/Robo-Rho/Rho kinase signal pathway, and to provide the new scientific evidence for EA treatment of PNI.

周围神经损伤（PNI）再生修复是现代医学热点难题之一，电针治疗有一定优势，但机制研究有待深入。我们前期研究注意到再生轴突靶向这一关键因素，发现电针能增强PNI轴突导向因子Slit1/2及其mRNA表达，而信号通路Slit/Robo与Rho/Rho激酶由srGAP介导交联，故推测电针治疗PNI可能与此有关。本课题在此基础上，以中医针灸理论为指导，复制大鼠PNI模型，从整体、组织、细胞和分子水平，采用Nuero-Dil在体神经示踪、免疫荧光、电镜、RT-PCR 和Western Blot等，应用信号抑制剂Robo-Fc、Y-27632阻断对比，动态观测电针环跳、足三里穴对相关各级关键分子Slit、Robo、srGAP、Cdc42、Rac1、RhoA的影响规律，探明电针是否通过调控“Slit/Robo-Rho/Rho激酶”信号通路促进PNI轴突靶向再生修复，为电针治疗PNI提供新的科学依据。

周围神经损伤（PNI）再生修复是现代医学热点难题之一，电针治疗有一定优势，但机制研究有待深入。本课题我们前期研究基础上，以中医针灸理论为指导，复制大鼠PNI模型，从整体、组织、细胞和分子水平，采用免疫组化、电镜、RT-PCR 和Western Blot等，应用信号抑制剂Y-27632阻断对比，动态观测电针环跳、足三里穴发现“Slit/Robo-Rho/Rho激酶”信号通路的相关各级关键分子Slit、Robo、srGAP、Cdc42、Rac1表达增强、RhoA表达减弱，slit表达高峰在第7d，其余指标则在第14d。本研究探明了电针促进PNI轴突靶向再生修复的部分机理，为电针治疗PNI提供新的科学依据。