LncRNAuc.48+对CGRP介导的三叉神经痛的作用  

Effect of LncRNAuc.48+on CGRP-mediated trigeminal neuralgi

作　　者：谭梦霞 吴饶平 张爱霞 高云[1] 熊伟[4] TAN Meng-xia;WU Rao-ping;ZHANG Ai-xia;GAO Yun;XIONG Wei(Dept of Physiology,Basic Medical College,Nanchang University,Nanchang 330006,China;Jiangxi Health Vocational College,Nanchang 330052,China;Nanchang Medical College,Nanchang 330052,China;Affiliated Stomatological Hospital of Nanchang University,Nanchang 330019,China)

机构地区：[1]南昌大学基础医学院生理学教研室,江西南昌330006 [2]江西卫生职业学院,江西南昌330052 [3]南昌医学院,江西南昌330052 [4]南昌大学附属口腔医院,江西南昌330019

出　　处：《中国药理学通报》2024年第10期1866-1871,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81860199,82360199);江西省教育厅科学技术研究项目(No GJJ205609)。

摘　　要：目的探究长链非编码核糖核酸uc.48+(long non-coding RNA,lncRNA uc.48+)如何影响三叉神经痛(trigeminal neuralgia,TN)大鼠三叉神经节(trigeminal ganglion,TG)中降钙素基因相关肽(calcitonin gene related peptide,CGRP)以及其潜在的作用机制。方法慢性压迫性损伤大鼠眶下神经(chronic compression injury to the infraorbital nerve,CCI-ION)建立大鼠TN动物模型。成模后,经眶下孔局部注射uc.48+小干扰敲低lncRNAuc.48+,以及向正常大鼠转染uc.48+质粒过表达lncRNAuc.48+。通过行为学来观察各组大鼠面部机械痛阈值(mechanical pain threshold,MWT),结合qPCR、蛋白印迹等方法观察大鼠TG中CGRP的含量及变化。ELISA法观察1L-1β的变动状况。结果接受uc.48+小干扰处理的TN大鼠机械痛敏阈值明显上升;TG中CGRP的蛋白、mRNA水平明显下降(P<0.01),1L-1β的水平也降低(P<0.01);此外,与正常大鼠相比,正常大鼠转染uc.48+质粒后,其机械痛敏阈值明显下降,TG中CGRP的蛋白、mRNA水平明显上升(P<0.01),1L-1β的水平明显增加(P<0.01)。结论TN大鼠敲除uc.48+显著减轻疼痛,而过表达uc.48+则加剧了TN的疼痛传导。uc.48+小干扰对TN有一定的抑制作用,该机制可能是通过减少神经病理痛大鼠TG中CGRP的表达,抑制初级感觉神经节对三叉神经病理痛信息的传播,进而减轻三叉神经病理痛对机械性疼痛的敏感性。Aim To investigate how the long non-coding RNA uc.48+(lncRNA uc.48+)affected calcitonin gene-related peptide(CGRP)in the trigeminal ganglion(TG)of rats with trigeminal neuralgia(TN)and its potential mechanism.Methods Chronic constriction injury of the infraorbital nerve(CCI-ION)in rats was used to create the animal model for trigeminal neuralgia.After modeling,uc.48+siRNA was injected locally via the infraorbital foramen to knock down lncRNA uc.48+,and uc.48+plasmid was transfected into normal rats to over-express lncRNA uc.48+.The face mechanical pain threshold(MWT)of each group was measured by behavioral test,and the content and changes of CGRP in rat TG were observed using qPCR and protein blotting.The change in serum inflammatory cytokine 1L-1βwas determined using ELISA.Results The MWT in TN rats treated with the uc.48+siRNA increased significantly,but the protein and mRNA levels of CGRP in TG decreased significantly(P<0.01),and the level of 1L-1βdecreased as well(P<0.01).In addition,the MWT of normal rats transfected with uc.48+plasmid was significantly diminished,and the mRNA and protein levels of CGRP in TG were markedly elevated(P<0.01),as were the levels of 1L-1β(P<0.01),compared to normal rats.Conclusions Knocking out uc.48+in TN rats reduces pain,while overexpressing uc.48+exacerbates pain transmission in trigeminal neuralgia.The mechanism by which uc.48+small interference inhibits trigeminal neural pathology pain may be through decreasing CGRP expression in TG of rats with TN,therefore ameliorating mechanical pain sensitivity.

关 键 词：长链非编码核糖核酸uc.48+ 三叉神经痛 降钙素基因相关肽 三叉神经节 小干扰 过表达 

分 类 号：R-332[医药卫生] R342.2R341.6R745.11R977.6