电针调控lncRNA及其致痛靶基因Rpl29治疗带状疱疹后遗神经痛的机制

Electroaupuncture (EA) has significant clinical effect in treatment of postherpetic neuralgia, but the mechanisms are not well understood. Lacking of evidence-based medicine hindered the popularization of acupuncture. Recent studies indicated that lncRNA modulate gene expression at the epigenetic, transcriptional and post-transcriptional level and participate in the modulation of neuropathic pain. In the previous study of this project, EA alter the expression of lncRNA in the spinal cord of PHN rat model，and successfully predicted the target gene（Rpl29）which is closely related to the expression of lncRNA. This project plan to verify the lncRNA and its target genes involved in the PHN model and modulated by EA in vitro and vivo. Further, to observe the changes of lncRNA and its target gene expression at different time points of EA treatment. Moreover, use RNA pull-down to observe the regualation of lncRNA and its target genes. However, EA play a role in analgesic effect by modulating the interaction of lncRNA and its target genes. This project plan illustrate the mechanisms of Immediate effects and cumulative effects of EA treatment PHN by modulating lncRNA, to provide the experimental evidence for the treatment of neuropathic pain and the scientific basis for the internationalization, modernization of EA

电针（electroacupuncture）治疗带状疱疹后遗神经痛（PHN）在临床疗效显著，但鲜有涉及机理的研究，缺乏循证医学依据，阻碍了针灸普及。新近研究表明，lncRNA能在表观遗传、转录及转录后水平调控基因表达，参与神经病理痛的调控过程，本项目前期工作发现，电针对PHN模型大鼠脊髓背角差异表达的lncRNA具有翻转作用，并成功预测了参与PHN的特定lncRNA密切关系的致痛靶基因Rpl29。本项目拟通过细胞和整体水平对电针调控的参与PHN模型的lncRNA及其致痛靶基因进行验证，进一步观察电针不同时间点lncRNA及其致痛靶基因表达变化，采用RNA pull-down技术探索lncRNA及其靶基因Rpl29的机制。本项目拟深入阐明电针通过调控lncRNA治疗PHN的即时效应和累积效应的机制，为临床运用电针防治神经病理性疼痛疾病提供科学的实验依据，也为电针现代化、国际化提供科学依据。

目前，带状疱疹后遗神经痛（postherpetic neuralgia, PHN）是疼痛医学界的难题，且发病率逐年增加，是危害中老年人健康的潜在因素。电针（electroacupuncture，EA）治疗PHN 在临床疗效显著，但鲜有涉及机理的研究，只突出实用性，缺乏科学性、规范性，缺乏循证医学依据，阻碍了针灸的普及。本项目前期工作发现，电针对PHN模型大鼠脊髓背角netrin-1及其受体UNC5H2、DCC的表达均有调节作用，而且电针通过激活μ-阿片受体抑制netrin-1及其受体UNC5H2、DCC引起的有髓神经纤维的长芽，从而缓解神经病理痛，为我们临床采用电针治疗带状疱疹后遗神经痛提供了理论依据。新近研究表明，lncRNA能在表观遗传、转录及转录后水平调控基因表达，参与神经病理痛的调控过程。本项目通过基因芯片技术，筛选出电针参与神经病理性疼痛的基因及其lncRNA。发现外周DRG上 Ciart、Csf1、α2δ1是电针治疗CCI诱导的神经病理痛的靶基因，lncRNA LOC100912617只参与CCI诱导的神经病理性疼痛。初步阐明，电针缓解神经病理性疼痛可能是通过调节昼夜节律、抑制炎症、促进损伤修复等方面实现的。本项深入阐明电针通过调控lncRNA及其靶基因治疗PHN的机制，为临床运用电针防治神经病理痛相关疾病提供科学依据，有助于电针的现代化、国际化，具有较重要的理论和实际意义。