基于BDNF-TrkB/proBDNF-p75^(NTR)信号通路探讨电针治疗脊髓损伤的分子机制  

Probe into the Molecular Mechanism of Electroacupunture Therapy for Spinal Cord Injury Bastd on the BDNF-TrkB/proBDNF-p75^(NTR)Signaling Pathway

作　　者：叶青[1] 时素华[1] 姚海江[1] 胡煜 曹祖懋 李志刚[1] YE Qing;SHI Suhua;YAO Haijiang;HU Yu;CAO Zumao;LI Zhigang(Beijing University of Chinese Medicine,Beijing,China,100029)

机构地区：[1]北京中医药大学,北京100029

出　　处：《河南中医》2023年第7期1100-1106,共7页Henan Traditional Chinese Medicine

基　　金：国家自然科学基金项目(8200153010)。

摘　　要：电针治疗脊髓损伤可以显著提高脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)、原肌球蛋白受体激酶B(tropomyosin-receptor kinase,TrkB)蛋白的表达,下调p75神经营养素受体(p75 neurotrophin receptor,p75^(NTR))蛋白的表达。电针可以通过提高BDNF促进神经元的存活、促进受损纤维的再生、促进神经可塑性、促进髓鞘形成BDNF基因修饰的成纤维细胞。BDNF诱导的TrkB信号可能通过四种主要的细胞内途径影响突触可塑性、轴突生长、存活和细胞内阳离子平衡:(1)经磷脂酰-3激酶(P1-3K)/Akt通路促进神经元树突分枝和树突棘生成,影响突触生长和结构形成。(2)受体诱导小分子GTP酶Ras的激活,经过一系列复杂的磷酸化过程,最终激活许多细胞外信号调节激酶(extracellular signal-regulated Kinase,ERK)途径并对环腺苷3′,5′-单磷酸含量进行调节促进轴突生长。(3)经磷脂酶C-γ(Phospholipase C-γ,PLC-γ)/肌醇3-磷酸(inositol triphosphate,IP-3)通路参与Ca^(2+)的调控,促进Ca^(2+)从细胞内储存释放,促进突触可塑性等。(4)此外通过N-甲基-D-天冬氨酸(N-Methyl-D-aspartic acid,NMDA)受体的磷酸化,TrkB信号可能导致钙和钠内流的增加。故电针治疗脊髓损伤,可使BDNF与TrkB高亲和力结合,促进脊髓损伤的修复。其可能是通过激活BDNF-TrkB信号通路,抑制BDNF前体(brain-derived neurotrophic factor precursor,proBDNF)-p75^(NTR)信号通路来实现对神经的再生修复。Electroacupuncture treatment of spinal cord injury can significantly increase the expression of brain-derived neurotrophin(BDNF),tropomyosin receptor kinase B(TrkB)protein,and down-regulate the expression of p75 neurotrophin receptor(p75^(NTR))protein.Electroacupuncture can promote the survival of neurons,the regeneration of damaged fibers,neuroplasticity,and the formation of BDNF gene modified fibroblasts by increasing BDNF.BDNF-induced TrkB signaling may affect synaptic plasticity,axon growth,survival and intracellular cation balance through the following four main intracellular pathways:(1)It can promote neuronal dendritic branching and dendritic spine generation via phosphatidyl-3 kinase(P1-3K)/Akt pathway,and affect synaptic growth and structure formation.(2)The receptor induces the activation of small molecule GTP enzyme Ras,which undergoes a series of complex phosphorylation processes,ultimately activating many extracellular signal-regulated kinase(ERK)pathways and regulating the content of cyclic adenosine 3',5'-monophosphate to promote axonal growth.(3)TrkB signaling via phospholipase C-(PLC-)/Inositol 3-phosphate(IP-3)pathway participates in the regulation of Ca^(2+),promotes therelease of Ca^(2+) from intracellular storage,and promotes synaptic plasticity.(4)In addition,TrkB signaling may lead to the increase of calcium and sodium influx through the phosphorylation of N-methyl-D-aspartic acid(NMDA)receptor.Therefore,electroacupuncture treatment for spinal cord injury can bind BDNF with TrkB with high affinity,promoting the repair of spinal cord injury.It may be achieved by activating the BDNF-TrkB signaling pathway and inhibiting the brain-derived neurotropic factor precursor(proBDNF)-p75^(NTR)signaling pathway to achieve nerve regeneration and repair.

关 键 词：脊髓损伤 电针疗法 脑源性神经营养因子 原肌球蛋白受体激酶B 脑源性神经营养因子前体 p75神经营养素受体 

分 类 号：R245.319[医药卫生—针灸推拿学]