嘌呤能受体3通过p38丝裂原活化蛋白激酶信号通路参与大鼠三叉神经痛的维持  

Purinergic receptor 3 is involved in the maintenance of trigeminal neuralgia through the p38 mitogen-activated protein kinase signaling pathway in rats

作　　者：王祥 贺建东 韩冲芳 杨文曲 陈建平 段丽珍 贾晓飞 Wang Xiang;He Jiandong;Han Chongfang;Yang Wenqu;Chen Jianping;Duan Lizhen;Jia Xiaofei(Department of Pain Medicine,Shanxi Bethune Hospital,Third Hospital of Shanxi Medical University,Taiyuan 030032,China;Department of Anesthesiology,Shanxi Bethune Hospital,Third Hospital of Shanxi Medical University,Taiyuan 030032,China)

机构地区：[1]山西白求恩医院山西医科大学第三医院疼痛科,太原030032 [2]山西白求恩医院山西医科大学第三医院麻醉科,太原030032

出　　处：《中华实验外科杂志》2024年第7期1453-1456,共4页Chinese Journal of Experimental Surgery

基　　金：山西省基础研究计划项目(202103021223410)。

摘　　要：目的探讨嘌呤能受体3(P2X3R)通过p38丝裂原活化蛋白激酶(p38 MAPK)/核因子-κB(NF-κB)信号通路对三叉神经痛(TN)大鼠炎性反应的影响及其机制。方法采用随机数字表法将SD大鼠分为4组, 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+P2X3R特异性拮抗剂A-317491组(TN+A-317491组), 每组12只。采用三叉神经眶下支慢性缩窄术制备TN模型。TN+A-317491组大鼠于造模后3、7、10和14 d时, 腹腔注射A-317491(0.5 mg/kg);TN+NS组大鼠造模后腹腔注射等剂量生理盐水。于造模前1 d、造模后3、7、10、14和28 d(T0~5)时测定面部机械痛阈(MWT)。造模28 d后, 处死大鼠取三叉神经组织, 蛋白质印迹法(Western blot)检测P2X3R、p38MAPK、p-p38MAPK、p-NF-κB p65的表达;酶联免疫吸附(ELISA)法检测肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β和IL-6的含量;苏木精-伊红(HE)染色观察三叉神经组织病理变化。组间差异比较采用t检验和单因素方差分析。结果 TN组T1~5时MWT低于S组, T2~5时MWT低于TN+A-317491组。TN组P2X3R、p-p38MAPK、p-NF-κB p65表达高于S组和TN+A-317491组(0.68±0.05比0.42±0.03、0.44±0.05, F=62.838, P<0.05;0.84±0.01比0.48±0.05、0.49±0.06, F=165.036, P<0.05;0.88±0.03比0.53±0.05、0.56±0.09, F=56.481, P<0.05)。TN组TNF-α、IL-1β、IL-6含量高于S组和TN+A-317491组[(33.78±1.89) pg/ml比(15.20±1.33)、(22.02±2.30) pg/ml, F=44.956, P<0.05;(41.92±3.03) pg/ml比(21.82±1.95)、(30.71±3.58) pg/ml, F=81.745, P<0.05;(32.62±1.52) pg/ml比(17.63±1.27)、(23.50±1.83) pg/ml, F=65.971, P<0.05]。TN组和TN+NS组三叉神经组织病理学损伤重于S组, TN+A-317491组病理学损伤轻于TN组和TN+NS组。结论 P2X3R参与大鼠TN的维持, 可能与激活p38MAPK/NF-κB信号通路后, 炎性反应增加有关。Objective To investigate the effects of purinergic receptor 3(P2X3R)on the inflamma-tory response in trigeminal neuralgia rats through the p38 mitogen-activated protein kinase(p38 MAPK)/nuclear factor-kB(NF-kB)signaling pathway and its mechanism.Methods SD rats were divided into 4 groups using a randomized numeric table method:sham operation group(S group),trigeminal neuralgia group(TN group),trigeminal neuralgia+saline group(TN+NS group),and trigeminal neuralgia+P2X3R-specific antagonist A-317491 group(TN+A-317491 group).A trigeminal neuralgia model was prepared using chronic constriction injury of the infraorbital nerve.Rats in the TN+A-317491 group were injected intraperitoneally with A-317491(0.5 mg/kg)at 3,7.,10,and 14 d after modeling;rats in the TN+NS group were injected intraperitoneally with an equal dose of saline.Facial mechanical pain withdraw thresh-old(MWT)was measured at 1st d before modeling,and at 3rd,7th,10th,14th,and 28th d after model-ing(T0-5).After 28 d of modeling,the trigeminal nerve tissues were taken from the executed rats,and the expression levels of P2X3R,p38MAPK,P-p38MAPK,p-NF-kB p65 were detected by Western blotting method.The contents of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 were detected by enzyme linked immunosorbent assay(ELISA).The pathological changes of trigeminal nerve tissues were observed by hematoxylin and eosin(HE)staining.The differences between groups were compared using ttests and one-way ANOVA.Results MWT was lower in the TN group at T1-5 than in the S group,and that in the TN group at T2-5 than in the TN+A-317491 group.The expression of P2X3R,P-p38 MAPK and p-NF-kB p65 were up-regulated in the TN group compared to the S group and TN+A-317491 group(0.68±0.05 vs.0.42±0.03,0.44±0.05,F=62.838,P<0.05;0.84±0.01 vs.0.48±0.05,0.49±0.06,F=165.036,P<0.05;0.88±0.03 vs.0.53±0.05,0.56±0.09,F=56.481,P<0.05).There was an increase of TNF-α,IL-1βand IL-6 contents[(33.78±1.89)vs.(15.20±1.33),(22.02±2.30)pg/ml,F=44.956,P<0.05;(41.92±3.03)vs.(21.82

关 键 词：三叉神经痛 受体 嘌呤能P2 p38丝裂原活化的蛋白激酶类 炎性反应 核因子-ΚB 

分 类 号：R745.11[医药卫生—神经病学与精神病学]