遗传性癫痫伴热性惊厥附加症小鼠STAT3和CXCL8的表达与分析  

Analysis on the Expression Levels of STAT3 and CXCL8 in Genetic Epilepsy with Febrile Seizures Plus(GEFS+)Mice

作　　者：姜啸风[1] 凌寅杰 袁琛[2] 吕正兵[1] JIANG Xiao-feng;LING Yin-jie;YUAN Chen;LüZheng-bing(School of Life Science and Technology,Zhejiang Sci-Tech University,Hangzhou 310018,China;Huzhou No.1 People's Hospital of Pediatrics,Huzhou 313099,China)

机构地区：[1]浙江理工大学生命科学与医药学院,浙江杭州310018 [2]湖州市第一人民医院儿科,浙江湖州313099

出　　处：《药物生物技术》2021年第6期569-573,共5页Pharmaceutical Biotechnology

基　　金：浙江省基础公益研究计划支持(No.LGF18H090012)。

摘　　要：为探明遗传性癫痫伴热性惊厥附加症(GEFS+)小鼠外周血中STAT3和CXCL8的表达情况,并探究STAT3/CXCL8通路活化程度与GEFS+癫痫发作之间的关系,选取2月龄C57BL/6小鼠16只,雌雄各半,每只小鼠经由腹腔注射戊四唑(PTZ,55 mg/kg)造模为GEFS+症状小鼠(实验组),经异氟烷麻醉后植入电极获取脑电波(EEG)信号。同时选取正常2月龄C57BL/6小鼠16只作为对照。应用实时荧光定量PCR和蛋白印迹等技术检测外周血STAT3和CXCL8的表达情况差异及EEG信号的差异并进行统计学分析。实验组小鼠外周血中STAT3和CXCL8的转录水平较对照组相比分别显著上升了(5.81±0.84)倍和(42.65±5.70)倍,蛋白表达水平较对照组相比也分别显著上升了(2.11±0.34)倍和(13.61±3.15)倍,具有统计学意义(P<0.01);与对照组相比,实验组小鼠异常癫痫发作电信号显著增强,痫性活动明显,出现较多尖锐的连续棘波。GEFS+症状小鼠的外周血中STAT3和CXCL8的表达增加明显,表明STAT3和CXCL8的高表达与癫痫发作有一定关联性;STING-STAT3/CXCL8通路在GEFS+病理过程中存在潜在的调控机理,该通路的活化可能参与了促进癫痫发作的病理过程。本研究初步阐明了免疫炎症与癫痫的关系,为癫痫尤其是难治性癫痫的靶向治疗提供新的思路与实验依据。To evaluate the expression levels of STAT3 and CXCL8 in Genetic epilepsy with febrile seizures plus(GEFS+)mice's peripheral blood samples,and the relevance between the activation of STAT3/CXCL8 pathway and the epileptic seizure in GEFS+mice have also been evaluated.16 C57BL/6 mice of 2-month age,half male and half female,were ip injected by pentylenetetrazol(PTZ,55 mg/kg)molding for GEFS+mice(Experiment group),the electrodes had been planted to pick up the brain waves(EEG)signal after anesthesia with isoflurane,another group of 16 C57BL/6 mice of 2-month age was set as control.The real-time QPCR and western blot were used for detecting the expression levels of STAT3 and CXCL8 in peripheral blood samples,and the EEG signals were also analyzed using method of statistics.The transcriptional levels of STAT3 and CXCL8 in experiment group were(5.81±0.84)times and(42.65±5.70)times higher than those in the control group,respectively,the expression levels of STAT3 and CXCL8 in experiment group were also(2.11±0.34)times and(13.61±3.15)times higher than those in the control group,respectively.The results have statistical significance(P<0.01).GEFS+mice showed a significant stronger abnormal epileptic seizure electrical signal,the epileptic activity is evident,the larger number of sharp continuous spike waves were also detected in GEFS+mice.The expression levels of STAT3 and CXCL8 in GEFS+mice showed significant increase than control mice,the high expression of STAT3 and CXCL8 may play an important role in epileptic seizure.STING-STAT3//CXCL8 pathway has a potential regulatory mechanism in GEFS+pathological process.The activization of STAT3/CXCL8 pathway may involve in the promotion of the pathological process of epileptic seizures.Elucidating the relationship between immune inflammation and epilepsy can provide new ideas and experimental basis for targeted therapy of epilepsy,especially for refractory epilepsy and so on.

关 键 词：遗传性癫痫伴热性惊厥附加症 STAT3 CXCL8 癫痫发作 靶向治疗 免疫因子 

分 类 号：R742.3[医药卫生—神经病学与精神病学]