肿瘤坏死因子α对背根神经节电压门控性钠通道表达的影响  

Effect of TNF-α on Expression of Nav1.3 Channels in Dorsal Root Ganglion

作　　者：臧颖[1] 何昕华[1] 庞瑞萍[1] 魏绪红[1] 信文君[1] 周利君[1] 李永勇[1] 刘先国[1] 

机构地区：[1]中山大学疼痛研究中心∥中山医学院生理学教研室,广东广州510080

出　　处：《中山大学学报（医学科学版）》2010年第5期597-601,共5页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金青年基金(30900436)

摘　　要：【目的】探讨肿瘤坏死因子α(TNF-α)对背根神经节(DRG)电压门控性钠通道(Nav1.3)表达的影响,并探讨其在神经病理性疼痛形成中的可能作用。【方法】采用免疫荧光组织化学方法和免疫荧光细胞化学方法,观察外源性重组TNF(rrTNF)对在体大鼠和离体培养的大鼠DRG神经元Nav1.3表达的影响。【结果】①不损伤任何神经,仅在大鼠坐骨神经周围给予100pg/mL的rrTNF可引起病理性疼痛的产生,并引起L5和L4DRG神经元内Nav1.3显著上调;②在分离培养的正常成年大鼠DRG神经元表面直接给予100pg/mLrrTNF显著诱导Nav1.3表达上调,其上调分布于DRG神经元的胞膜和胞浆,并以胞膜上调更为显著。【结论】TNF-α在神经病理性疼痛形成中具有重要作用,外周神经损伤可能通过DRG内TNF-α的上调,促发Nav1.3异常表达,由初级感觉传入异常兴奋,参与病理性疼痛的产生。Objective To discuss the effect of TNF-α on the expression of tetraodontoxin-sensitive Nav1.3 channels in dorsal root ganglion（DRG） and further to explain the mechanism resided in the development of neuropathic pain.Method With use of the methods of immunohistochemistry and immunocytochemistry,the effect of recombinant rat TNF-α（rrTNF） on the expression of Nav1.3 in DRG neurons was investigated in vivo and in vitro.Result Peri-sciatic administration of rrTNF without any nerve injury,which produced lasting mechanical allodynia,up-regulated Nav1.3 in L4 and L5 DRG neurons in vivo.rrTNF at the concentrations of 100 pg/mL increased the expression of Nav1.3 in cultured adult rat DRG neurons.The disposition of Nav1.3 is located in cytoplasm and membrane,especially in membrane.Conclusion These data suggested that increased TNF-α in DRG neurons may contribute to neuropathic pain by induction of the over-expression of Nav1.3 channels.

关 键 词：肿瘤坏死因子-Α 钠通道 背根神经节 病理性疼痛 

分 类 号：R338.7[医药卫生—人体生理学]