[1]汪 逵,潘 轲,邬 立.Gm14461通过招募CSTF2上调CGRP和P2X3/7受体表达促进三叉神经痛的作用机制研究[J].现代检验医学杂志,2025,40(03):18-23,36.[doi:10.3969/j.issn.1671-7414.2025.03.004]
　WANG Kui,PAN Ke,WU Li.Study on the Mechanism of Gm14461 Promoting Trigeminal Neuralgia by Recruiting CSTF2 to Upregulate CGRP and P2X3/7 Receptor Expression[J].Journal of Modern Laboratory Medicine,2025,40(03):18-23,36.[doi:10.3969/j.issn.1671-7414.2025.03.004]
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Gm14461通过招募CSTF2上调CGRP和P2X3/7受体表达促进三叉神经痛的作用机制研究()

《现代检验医学杂志》[ISSN:/CN:]

卷:
第40卷
期数:
2025年03期
页码:
18-23,36
栏目:
论著
出版日期:
2025-05-15

文章信息/Info

Title:
Study on the Mechanism of Gm14461 Promoting Trigeminal Neuralgia by Recruiting CSTF2 to Upregulate CGRP and P2X3/7 Receptor Expression
文章编号:
1671-7414（2025）03-018-07
作者:
汪 逵，潘 轲，邬 立
（恩施土家族苗族自治州中心医院神经外科，湖北恩施 445000）
Author(s):
WANG Kui, PAN Ke, WU Li
(Department of Neurosurgery，Enshi Tujia and Miao Autonomous Prefecture Central Hospital，Hubei Enshi 445000，China)
关键词:
三叉神经痛; Gm14461; 裂解刺激因子2; 降钙素基因相关肽; P2X3/7受体
分类号:
R-332
DOI:
10.3969/j.issn.1671-7414.2025.03.004
文献标志码:
A
摘要:
目的研究长链非编码RNA（lncRNA）Gm14461促进三叉神经痛（TN）的作用及其潜在的可能分子机制。方法通过眶下神经慢性压迫损伤手术诱导建立TN小鼠模型，采用Gm14461的短发夹RNA（shRNA）注射TN小鼠，测量小鼠三叉神经节中Gm14461表达水平和机械痛阈值（MWT）。采用肿瘤坏死因子-α（TNF-α）诱导三叉神经节在体外建立TN细胞模型，采用sh-Gm14461和裂解刺激因子2（CSTF2）过表达载体（OE-CSTF2）处理三叉神经节。RNA免疫共沉淀（RIP）分析CSTF2与Gm14461，降钙素基因相关肽（CGRP）、嘌呤受体P2X3和P2X7mRNA的结合情况。结果与假手术组相比，TN组小鼠三叉神经节中Gm14461表达显著升高（t=35.450），小鼠MWT值呈时间依赖性降低（t=8.427～28.190），差异具有统计学意义（均P<0.05）；TN小鼠三叉神经节中炎症因子TNF-α，IL-1β，IL-6表达水平及疼痛相关蛋白CGRP，P2X3，P2X7水平显著升高，差异具有统计学意义（t=31.750～50.240，均P<0.05）。敲低Gm14461显著改善TN小鼠MWT（t=6.019～26.548），降低炎症因子（t=43.959,26.416,25.431）和疼痛相关蛋白水平（t=38.709,43.257,45.807），差异具有统计学意义（均P<0.05）。与对照组比较，TNF-α诱导的三叉神经节中Gm14461表达上调（t=27.710），炎症因子水平和疼痛相关蛋白表达水平显著升高（t=23.076～29.508），差异具有统计学意义（均P<0.05）。敲低Gm14461后，Gm14461表达水平降低（t=3.641），显著降低TNF-α诱导的三叉神经节中炎症因子和疼痛相关蛋白水平（t=20.560～25.136），差异具有统计学意义（均P<0.05）。Gm14461与CSTF2结合上调CSTF2蛋白水平，CSTF2蛋白上调分别与CGRP，P2X3，P2X7的mRNA结合并促进其表达。过表达CSTF2可逆转Gm14461敲低对TNF-α诱导的三叉神经节(TGs)中炎症反应和疼痛相关蛋白表达的抑制作用（t=18.870～24.399，均P<0.05）。结论Gm14461通过招募CSTF2上调CGRP，P2X3和P2X7表达，促进炎症反应，从而降低TN小鼠的机械痛阈值，促进疼痛。
Abstract:
Objective To investigate the role of long non coding RNA (lncRNA) Gm14461 in promoting trigeminal neuralgia (TN) and its potential molecular mechanisms. Methods A TN mouse model was induced by surgery for chronic compression injury of the infraorbital nerve. Short hairpin RNA (shRNA) of Gm14461 was injected into TN mice, and the expression level of Gm14461 and mechanical pain threshold (MWT) in the trigeminal ganglia of the mice were measured. A TN cell model was established in vitro using tumor necrosis factor - α (TNF-α) to induce trigeminal ganglia, and the trigeminal ganglia were treated with sh-Gm14461 and cleavage stimulation factor subunit 2 (CSTF2) overexpression vector (OE-CSTF2). RNA immunoprecipitation (RIP) analysis of CSTF2 binding to Gm14461, calcitonin gene-related peptide (CGRP), purine receptors P2X3 and P2X7 mRNA.Results Compared with the sham surgery group, the expression of Gm14461 in the trigeminal ganglia of TN group mice was significantly increased (t=35.450), and the MWT value of mice decreased in a time-dependent manner (t=8.427 ～ 28.190), with statistical significance (all P<0.05). The expression levels of inflammatory factors TNF - α, IL-1 β and IL-6, as well as pain related proteins CGRP, P2X3, and P2X7, were significantly increased in the trigeminal ganglia of TN mice, and the differences were statistically significant (t=31.750 ～ 50.240, all P<0.05). Knocking down Gm14461 significantly improved MWT (t=6.019 ～ 26.548), reduced inflammatory factors (t=43.959, 26.416, 25.431),

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备注/Memo

备注/Memo:
基金项目：湖北省自然科学基金（项目编号：2023AFD073）。
作者简介：汪逵（1986-），男，硕士，主治医师，研究方向：三叉神经痛发病机制，E-mail：Waangki@163.com。
通讯作者：潘轲（1974-），男，硕士，主治医师，研究方向：三叉神经痛发病机制，E-mail：1985680369@qq.com。
更新日期/Last Update: 2025-05-15