p38丝裂原活化蛋白激酶信号通路在三叉神经痛维持中的作用:大鼠实验研究
The role of p38 MAPK signal pathway in the maintenance of trigeminal neuralgia:an experimental study in rats
王祥 1韩冲芳 2杨文曲 2贺建东 2陈建平 1高翔 1张建文2
作者信息
- 1. 山西医科大学第三医院 山西白求恩医院疼痛科,太原市,030032
- 2. 山西医科大学第三医院 山西白求恩医院麻醉科,太原市 030032
- 折叠
摘要
目的 评价p38丝裂原活化蛋白激酶(p38MAPK)信号通路在大鼠三叉神经痛(TN)维持中的作用.方法 清洁级健康成年雄性SD大鼠48只,体重180～220 g,2～3月龄,采用随机数字表法分为4组(n=12):假手术组(S组)、三叉神经痛组(TN组)、三叉神经痛+生理盐水组(TN+NS组)和三叉神经痛+SB203580组(TN+SB203580组).TN组、TN+NS组、TN+SB203580组采用眶下神经慢性缩窄术造模,S组只暴露眶下神经,不结扎;TN+SB203580组大鼠造模前4 h腹腔注射SB203580.TN+NS组大鼠造模前4 h腹腔注射等剂量生理盐水.于造模前1 d、造模后1、2、3及4周(T0～T4)时测定面部机械痛阈(MWT).机械痛阈测定结束后,处死大鼠取三叉神经节,蛋白质印迹法检测p38 MAPK、p-p38 MAPK、p-NF-κB p65表达,ELISA法检测TNF-a、IL-1β和IL-6的含量.结果 与S组比较,TN组、TN+NS组和TN+SB203580组 T1～T4 时 MWT 降低,TNF-a、IL-1β 及 IL-6 含量升高(P＜0.05);TN 组、TN+NS组 p-p38 MAPK表达上调[(0.81±0.03)、(0.80±0.05)比(0.44±0.02),P＜0.05]和 p-NF-κB p65 表达上调[(0.74±0.08)、(0.77±0.08)比(0.45±0.07),P＜0.05].与 TN组和 TN+NS组比较,TN+SB203580组 T1～T4时 MWT升高,p-p38 MAPK 表达下调[(0.45±0.04)比(0.81±0.03)、(0.80±0.05),P＜0.05]和 p-NF-κB p65 表达下调[(0.44±0.05)比(0.74±0.08)、(0.77±0.08),P＜0.05],TNF-a、IL-1β及 IL-6含量降低(P＜0.05).结论 p38 MAPK信号通路参与大鼠三叉神经痛的维持,与上调p-NF-κB p65蛋白表达,增加炎症因子释放有关.
Abstract
Objective To evaluate the role of p38 MAPK signaling pathway in the maintenance of trigeminal neuralgia in rats.Methods Forty-eight clean grade healthy adult male SD rats,weighing 180-220 g and aged 2-3 months,were randomly divided into four groups(n=12):sham group(group S),trigeminal neuralgia group(group TN),trigeminal neuralgia+normal saline group(group TN+NS)and trigeminal neuralgia+SB203580 group(group TN+SB203580).The rats were modeled in group TN,TN+NS and TN+SB203580 by chronic constriction of the infraorbital nerve,while only exposed the infraorbital nerve without ligation in the group S.The rats received intraperitoneal injection of SB203580 in group TN+SB203580 and same dose of normal saline in group TN+NS 4 hours before the modeling.The mechanical paw withdrawal threshold(MWT)was measured at 1 d before the modeling and 1,2,3 and 4 weeks after the modeling(T0-T4).The rats were sacrificed and the trigeminal ganglia were sampling.The expression of p38 MAPK,p-p38 MAPK,p-NF-κB p65 were detected by Western blot and the contents of TNF-α,IL-1β and IL-6 were detected by ELISA.Results Compared with the group S,MWT was decreased and the content of TNF-α,IL-1β and IL-6 were increased in the group TN,group TN+NS and group TN SB203580 at T1-T4.The expression of p-p38 MAPK[(0.81±0.03),(0.80±0.05)vs.(0.44±0.02),P＜0.05]and p-NF-κB p65[(0.74±0.08),(0.77±0.08)vs.(0.45±0.07),P＜0.05]were up-regulated in the group TN and group TN+NS.Compared with the group TN and group TN+NS,MWT was increased at T1-T4,the expression of p-p38 MAPK[(0.45±0.04)vs.(0.81±0.03),(0.80±0.05),P＜0.05]and p-NF-κB p65[(0.44±0.05)vs.(0.74±0.08),(0.77±0.08),P＜0.05]were down-regulated,the content of TNF-α,IL-1β and IL-6 were reduced in the group TN+SB203580(P＜0.05).Conclusion p38 MAPK signal pathway is involved in the maintenance of trigeminal neuralgia in rats,which is related to the expression of the up-regulation of p-NF-κB p65 protein,and the increased release of inflammatory factors.
关键词
三叉神经痛/p38丝裂原活化蛋白激酶类/信号通路/炎症因子Key words
Trigeminal neuralgia/p38 mitogen-activated protein kinases/Signal channel/Inflammatory factor引用本文复制引用
基金项目
山西省基础研究计划(202103021223410)
出版年
2024
NETL
NSTL
万方数据