G蛋白偶联雌激素受体1对颞叶癫痫大鼠发作易感性的影响  

Influence of G protein-coupled estrogen receptor 1 in epilepsy susceptibility of temporal lobe epileptic rats

作　　者：左娣[1] 文玉军[1] 任晓璠 丁娜[1] 路光远 马琳 和祯泉[1] 牛建国[1] Zuo Di;Wen Yujun;Ren Xiaofan;Ding Na;Lu Guangyuan;Ma Lin;He Zhenquan;Niu Jianguo(Ningxia Key Laboratory of Craniocerebral Diseases,Ningxia Medical University,Yinchuan 750004,China;College of Pharmacy,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学宁夏颅脑疾病重点实验室,银川750004 [2]宁夏医科大学药学院,银川750004

出　　处：《中华神经医学杂志》2021年第7期656-661,共6页Chinese Journal of Neuromedicine

基　　金：宁夏高等学校科学技术研究项目(NGY2020041);宁夏回族自治区自然科学基金(2021AAC03153);2020年度宁夏医科大学校级科研项目(XT2020028)。

摘　　要：目的探讨G蛋白偶联雌激素受体1(GPER1)特异性激动剂G1、拮抗剂G15对癫痫大鼠发作易感性的影响。方法将60只大鼠按随机数字表法分为对照组、G1处理组、G15处理组,每组20只。后2组大鼠分别腹腔注射GPER1特异激动剂G1(10μg)、拮抗剂G15(40μg),连续注射12 d。3组大鼠均制备氯化锂-匹罗卡品癫痫模型。观察大鼠腹腔注射匹罗卡品后1 h内的行为学表现,每隔5分钟采用Racine分级评估癫痫发作严重程度,比较3组大鼠癫痫发作(Racine分级Ⅳ级)的潜伏期和不同时间点癫痫发作级别。使用脑电监测系统监测大鼠脑电图,记录匹罗卡品注射前10 min到注射后2 h的脑电数据,采用傅立叶变换(FFT)进行脑电的时频分析。比较3组大鼠脑电能量值的分布和癫痫持续状态20 min内θ、α波能量值的变化。结果(1)与对照组、G1处理组比较,G15处理组大鼠的癫痫发作潜伏期明显缩短,差异均有统计学意义(P<0.05)。注射匹罗卡品后15 min、20 min,G1处理组大鼠癫痫发作分级较对照组低,差异均有统计学意义(P<0.05)。注射匹罗卡品后15~35 min,G15处理组大鼠癫痫发作分级较对照组高,差异均有统计学意义(P<0.05)。(2)与对照组比较,G1处理组大鼠癫痫发作时脑电波幅较小,而G15处理组大鼠癫痫发作时间较早,且脑电波幅大、频率高。与对照组比较,G1处理组大鼠的脑电能量值变化不明显,而G15处理组大鼠在2 h内呈现出更高的脑电能量值。与对照组和G1处理组比较,G15处理组大鼠在癫痫持续状态20 min内θ、α波能量值明显增强,差异均有统计学意义(P<0.05)。结论GPER1的活性水平与癫痫发作易感性有关,特异性抑制GPER1活性可增强癫痫易感性,增大癫痫过程中特定频率波段的能量值。Objective To study the influence of G protein-coupled estrogen receptor 1(GPER1)specific agonist G1 and antagonist G2 in epilepsy susceptibility of temporal lobe epileptic rats.Methods Sixty rats were randomly divided into control group,G1 treatment group and G15 treatment group(n=20).Rats in the latter two groups were intraperitoneally injected with GPER1 agonist G1(10μg)or antagonist G15(40μg)for a consecutive 12 d.Lithium chloride pilocarpine epilepsy models were prepared in the 3 groups.The behavior manifestations of these rats were observed within 1 h of intraperitoneal injection of pilocarpine;Racine grading was used to evaluate the severity of epileptic seizures every 5 min;the latency of epileptic seizures(Racine grading IV)and epileptic seizure grading at different time points in the 3 groups were compared.The EEG monitoring was performed to these rats,and EEG data were recorded from 10 min before pilocarpine injection to 2 h after pilocarpine injection;EEG time-frequency was analyzed by Fast-Fourier transform(FFT);distribution of brain electrical energy and changes ofθandαwave energy during 20 min of epileptic status were compared among the 3 groups.Results(1)As compared with that in the control group and G1 treatment group,the latency of epileptic seizures in the G15 treatment group was significantly shortened(P<0.05);15 and 20 min after pilocarpine injection,the epileptic seizure grading of rats in G1 treatment group was statistically lower than that in control group(P<0.05);15-35 min after pilocarpine injection,the epileptic seizure grading of rats in G15 treatment group was significantly higher than that in control group(P<0.05).(2)As compared with those in the control group,rats in the G1 treatment group had smaller brain wave amplitude,while the rats in the G15 treatment group had earlier seizure time,larger brain wave amplitude and higher frequency.There were no obvious changes in the amount of brain electrical energy between the G1 treatment group and control group;while the amount of brain

关 键 词：G蛋白偶联雌激素受体1 癫痫 匹罗卡品 G1 G15 

分 类 号：R742.1[医药卫生—神经病学与精神病学]