长非编码RNAuc.48+在三叉神经痛中的作用研究

Trigeminal neuralgia (TN) is one of the most intense forms of facial pain characterized by recurrent attacks of lancinating pain in the trigeminal nerve distribution, and is the key problem of clinic pain treatment. Trigeminal ganglion (TG) plays an important role in the formation of TN. Our preliminary experiments showed that the expressions of calcitonin gene related peptide (CGRP) and P2X4 receptor in TG of TN rats are obviously higher than those in the control rats, indicating that CGRP and P2X4 receptor of TG are involved in pain transmission of TN. It is reported that expression change of long noncoding RNA (lncRNAs) and factors influencing lncRNAs expression are related with the nervous system diseases. Preliminary experiments also found that the expression of uc.48+, one of lncRNAs, in TGs of TN rats was significantly higher than that in control rats. The aim of the project is to study the effect of uc.48+ siRNA on TN mediated by CGRP and P2X4 receptor in TN rats, and to find its possible mechanism, and provide new experimental evidences for the prevention and treatment of TN.

三叉神经痛（TN）是三叉神经分布区域突发的刀割样阵痛为主要特征的严重的面部疼痛，是临床疼痛治疗的难点。三叉神经节(TG)在三叉神经痛形成中具有重要作用。预实验显示三叉神经痛大鼠TG降钙素基因相关肽（CGRP）和嘌呤受体2X4（P2X4）受体的表达明显高于对照组，表明TG的CGRP和P2X4受体参与三叉神经痛大鼠的痛觉传递。文献报道长非编码RNA（lncRNAs）表达水平改变及影响lncRNAs改变的因素与神经系统疾病发病相关。预实验发现长非编码RNA之一的uc.48+在三叉神经痛大鼠TG中表达较对照组明显增高。本项目研究uc.48+小干扰对三叉神经痛大鼠TG的CGRP和P2X4受体介导三叉神经痛的作用及可能机理，为三叉神经痛防治提供实验基础和治疗靶点。

三叉神经痛（trigeminal neuralgia TN）是最常见的面部神经痛，目前尚无理想的治愈方法。长非编码核糖核酸(long noncoding RNA, lncRNA)参与人类很多疾病基因调控，其表达的异常变化可能与神经系统疾病密切相关。嘌呤P2X7受体是ATP门控离子通道家族中的一员，研究表明其可能参与了痛觉信息的调制和传导。降钙素基因相关肽(Calcitonin gene - related peptide, CGRP)是一个传递痛觉信息的神经肽且有可能参与三叉神经痛的发生过程。本研究旨在观察长非编码核糖核酸uc.48+ siRNA对慢性压迫性损伤眶下神经(chronic constriction injury of the infraorbital nerve, ION-CCI)诱导形成的三叉神经痛模型大鼠的影响及可能机制，为防治三叉神经痛探索新方法。.重要结果和关键数据如下：1. uc.48+ 小干扰后，TN 大鼠面部机械痛敏显著性改善，同时TN 大鼠三叉神经节（trigeminal ganglion,TG）中升高的P2X7、CGRP表达明显降低。TN大鼠血清中IL-1β的表达水平与Sham 组比较明显升高，给予uc.48+ 小干扰处理后明显降低。与Sham 组比较，TN组中ERK1/2磷酸化程度明显增强，给予uc.48+ 小干扰处理后也明显降低。2. 过表达uc.48+之后，与正常大鼠相比过表达大鼠机械痛敏阈值明显降低，同时TG 中P2X7、CGRP表达水平明显增加。过表达大鼠血清IL-1β较正常大鼠明显增加，同时TG 中p-ERK1/2磷酸化水平也明显增加。3. 运用RNA结合蛋白免疫沉淀（RIP）检测结果显示P2X7被显著富集，说明P2X7受体可以特异性地与uc.48+ 相结合。.本项目表明lncRNA uc.48+ 可促进TG的P2X7、CGRP表达上调，导致IL-1β的水平升高，TG的ERK1/2磷酸化水平增强，进而影响三叉神经痛的痛觉传递，而使用uc.48+ 小干扰后可抑制其相应的以上表达，起到缓解疼痛的作用。以上结果对三叉神经痛防治提供了实验基础和治疗靶点。