吡仑帕奈调控MAPK信号通路抗偏头痛作用及其机制  

Effects of perampanel on MAPK signal pathway in nitroglycerin-induced migraine rats and its mechanism

作　　者：翟庆龄 谢丹娜 王凯新 王雪贞[1] 陈金波[1] 董晓梦[1] Zhai Qingling;Xie Danna;Wang Kaixin;Wang Xuezhen;Chen Jinbo;Dong Xiaomeng(Dept of Neurology,Binzhou Medical University Hospital,Binzhou 256600;Binzhou Medical University,Yantai 264000)

机构地区：[1]滨州医学院附属医院神经内科,滨州256600 [2]滨州医学院,烟台264000

出　　处：《安徽医科大学学报》2022年第11期1725-1731,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81400903);山东省自然科学基金(编号:ZR2017LH032);山东省医药卫生科技发展计划项目(编号:2019WS322)。

摘　　要：目的探讨吡仑帕奈调控丝裂原活化蛋白激酶通路(MAPK)信号通路对偏头痛大鼠的影响。方法40只雄性SD大鼠随机分4组,每组10只:空白(生理盐水)组、硝酸甘油(NTG)组、吡仑帕奈50μg/kg+NTG预防组、吡仑帕奈100μg/kg+NTG预防组。观察大鼠挠头时间、爬笼次数,纤维丝测定大鼠眶周痛阈值,明暗箱实验观察大鼠畏光情况。免疫荧光法检测大鼠三叉神经节(TG)垂体腺苷酸环化酶激活肽(PACAP)表达水平,Western blot法检测大鼠TG中PACAP、磷酸化p38丝裂原活化蛋白激酶(p-p38MAPK)、磷酸化c-Jun氨基末端激酶(p-JNK)、磷酸化细胞外调节蛋白激酶(p-ERK)蛋白的表达水平,实时荧光定量聚合酶链反应法(RT-qPCR)测定PACAP mRNA的表达水平,酶联免疫吸附测定法(ELISA)检测大鼠血液中PACAP的浓度。结果与空白组相比,NTG组大鼠眶周痛阈降低,爬笼行为与梳理面部行为时间长,进入明室时间缩短,PACAP mRNA及蛋白相对表达量升高(P<0.05);与NTG组相比,吡仑帕奈50μg/kg+NTG预防组、吡仑帕奈100μg/kg+NTG预防组眶周痛阈提高,爬笼行为与梳理面部行为时间短,进入明室时间延长,PACAP mRNA及蛋白相对表达量降低(P<0.05)。与空白组相比,NTG组的p-p38MAPK、p-ERK、p-JNK相对表达量升高(P<0.05);与NTG组相比,吡仑帕奈预防组的p-p38MAPK、p-ERK、p-JNK相对表达量降低(P<0.05)。结论吡仑帕奈可能通过抑制MAPK信号传导通路缓解偏头痛症状。Objective To explore the effect of perampanel regulation of mitogen actived protein kinase(MAPK)signaling pathway after injection of nitroglycerin(NTG)induced migraine rats.Methods Thirty-two male SD rats were randomly divided into four groups with eight in each group:normal saline,NTG group,perampanel 50μg/kg+NTG group,perampanel 100μg/kg+NTG group.The time of scratching the head and the number of climbing the cage were observed,the periorbital pain threshold of the rat was measured by the fiber filament,and the photophobia of the rat was observed in the light and dark box experiment.Immunofluorescence was used to detect the rat TGs PACAP expression level;RT-qPCR was used to determine the expression level of PACAP mRNA and ELISA was used to detect the concentration of PACAP in rat blood.Meanwhile,Western blot was used to detect p-p38MAPK,p-JNK,p-ERK protein expression level in rats TG.Results Compared with the control group,the periorbital withdrawal threshold decreased,the cage climbing behaviors and facial grooming behaviors increased,and the time spent in the light compartment in the light-aversive behaviors decreased in the NTG group,the expression levels of PACAP mRNA and protein increased(P<0.05).While,the perampanel 50μg/kg+NTG group and the perampanel 100μg/kg+NTG group increased the periorbital withdrawal threshold,reduced the cage climbing behaviors and facial grooming behaviors,increased the time spent in the light compartment and decreased the expressions of PACAP mRNA and protein in comparison with the NTG group(P<0.05).Compared with the control group,the expression levels of p-p38MAPK,p-ERK and p-JNK in NTG group increased(P<0.05);compared with the NTG group,the expression levels of p-p38MAPK,p-ERK and p-JNK decreased in perampanel 50μg/kg+NTG group and the perampanel 100μg/kg+NTG group(P<0.05).Conclusion Perampanel may relieve migraine symptoms by inhibiting MAPK signaling pathway.

关 键 词：偏头痛 信号传导通路 吡仑帕奈 垂体腺苷酸环化酶激活肽 丝裂原活化蛋白激酶通路 

分 类 号：R741.02[医药卫生—神经病学与精神病学]