microRNA30b/96/182调控电压门控钠离子通道1.7参与神经病理性疼痛的作用机制

SCN9A基因编码的钠离子通道1.7亚基（Nav1.7）在神经病理性疼痛的发生发展中具有重要作用。减少Nav1.7表达量及活性可降低神经元的兴奋性，缓解疼痛。microRNA广泛表达于生物体内，与疼痛密切相关。课题组通过生物信息学查找发现miR-30b/96/ 182与SCN9A密切相关。据此提出假说: 外周神经损伤，miR-30b/96/182表达下调，SCN9A 转录后抑制减少，Nav1.7表达增加，神经元兴奋性增强，引起脊髓P物质和谷氨酸等神经递质释放增加，进一步传递信号，最终导致疼痛。本项目拟建立坐骨神经分支选择性损伤疼痛模型，通过过表达或沉默miR-30b/96/182表达，探讨其与SCN9A的作用关系。通过构建病毒载体，上调miR-30b/96/182，观察Nav1.7和神经元电生理的变化及痛敏情况，明确miR-30b/96/182的镇痛效应，为疼痛治疗提供新思路。

SCN9A gene encodes the ? subunit of sodium channel 1.7（Nav1.7）, which plays an important role in neuropathic pain. Its mutation has a close relation with three congenital diseases of paresthesia. MicroRNAs widely expresse in organisms and are closely related to the pain. Bioinformatics analysis revealed that miR-30b/96/182 are closely related to SCN9A.Therefore, we hypothesized that perpheral nerve injury might down regulate miR-30b/96/182 expression which make SCN9A lose post-transcriptional suppression. Nav1.7 expression increasing enhances neuronal excitability, causing the release of neurotransmitters such as substance P and glutamate in spinal cord. Signal transduction ultimately results in pain. In the present study, a rat neuropathic pain model established by the sciatic nerve injury are used. We will examine the relationship between SCN9A and miR-30b/96/182 by overexpression or knocking down miR-30b/96/182. To determine the analgesic effect of miR-30b/96/182, we detect changes of Nav1.7, neuronal electrophysiological and hyperalgesia by building viral vectors carrying miR-30b/96/182, which provide new ideas for the pain treatment.