普瑞巴林对颞叶癫痫大鼠睡眠结构的影响

Effect of pregabalin on sleep structure of rats with temporal lobe epilepsy

目的研究抗癫痫发作药物普瑞巴林单药治疗对匹罗卡品诱发的大鼠颞叶癫痫睡眠结构的影响。方法12只成年SD大鼠(雄雌各半)腹腔注射匹罗卡品建立慢性颞叶癫痫模型后,按照性别匹配原则分为模型组和普瑞巴林组,每组6只,雄雌各半。另取6只SD大鼠(雄雌各半)作为对照组。给大鼠安置颅骨电极,休息1周后开始视频与神经电生理监测。普瑞巴林组大鼠腹腔注射50 mg/kg普瑞巴林,模型组及对照组大鼠腹腔注射等体积生理盐水,15 min后开始记录各组大鼠的脑电图及肌电图。记录时间为10∶00~17∶00,连续记录2 d。观察各组癫痫发作次数、脑电图与肌电图变化情况。采用SPSS 25.0统计软件进行数据分析,多组间比较采用单因素方差分析,进一步两两比较采用Tukey检验和Games-Howell检验。结果(1)普瑞巴林组大鼠癫痫发作次数[0.0(0.0,1.0)次]显著低于模型组[2.5(1.0,4.8)次](Z=-3.0,P<0.05)。(2)脑电图记录7 h内大鼠睡眠情况,结果显示,对照组、模型组和普瑞巴林组三组大鼠的睡眠-觉醒各期转换次数、慢波睡眠(slow wave sleep,SWS)期持续时间、快速眼动睡眠(rapid eye movement,REM)期持续时间、SWS总时间、REM总时间和总睡眠时间均差异有统计学意义(F=10.5,4.1,13.0,7.8,4.4,9.3,均P<0.05)。普瑞巴林组[(66.3±18.0)次]和对照组[(87.8±14.1)次]大鼠的睡眠-觉醒各期转换次数均低于模型组[(106.7±20.8)次](均P<0.05)。普瑞巴林组大鼠的SWS期持续时间[(11.2±4.0)min]显著高于模型组[(5.9±1.8)min](P<0.05),模型组大鼠的SWS期持续时间则低于对照组[(7.7±1.2)min](P<0.05)。模型组大鼠REM期持续时间[(1.9±0.4)min]少于对照组REM期持续时间[(2.5±0.4)min](P<0.05),普瑞巴林组大鼠的REM期持续时间与模型组相比差异无统计学意义(P>0.05)。观测的7 h内,普瑞巴林组大鼠SWS总时间[(296.5±37.1)min]、总睡眠时间[(338.4±33.3)min]均高于模型组[SWS总时间(258.1±38.4)min,总睡眠时间(288.9±41.0)min](均P<0.05)。模型组大鼠REM总时间[(30.4±11.1)min]、总睡眠时间[(288.9±41.0)min]均显著少于对照组[REM总时间(50.2±8.5)min,总睡眠时间(339.0±19.6)min](P<0.05)。结论普瑞巴林单独使用可减少癫痫发作,同时改变癫痫引起的睡眠结构紊乱,主要表现在减少睡眠-觉醒各期转换次数,延长SWS期持续时间,增加睡眠持续性,增加SWS和总睡眠时间,提高睡眠质量。

Objective To explore the effect of pregabalin on sleep structure in rats with temporal lobe epilepsy induced by pilocarpine.Methods Twelve adult SD rats(half male and half female)were injected intraperitoneally with pilocarpine to establish a chronic temporal lobe epilepsy model.According to the principle of gender matching,they were divided into model group and pregabalin group,with 6 rats in each group(half male and half female).Another 6 SD rats(half male and half female)were taken as the control group.The skull electrodes were placed in the brain areas of rats to monitor the cerebral electrical activity,then recorded the data after resting for 1 week.Rats in pregabalin group were intraperitoneally injected with 50 mg/kg pregabalin while the rats in model group and control group were intraperitoneally injected with equal volume of normal saline.Fifteen minutes later,video electroencephalogram(EEG)and electromyogram(EMG)of rats in each group were recorded.The recording time was from 10∶00 to 17∶00 for 2 consecutive days.The seizure frequency,EEG and EMG were obtained.SPSS 25.0 was used for data analysis,one-way ANOVA was used for multi group comparison,and Tukey test and Games-Howell test were used for further pairwise comparison.Results(1)The frequency of seizures in the pregabalin group(0.0(0.0,1.0)times)were significantly lower than that in the model group(2.5(1.0,4.8)times)(Z=-3.0,P<0.05).(2)During the 7 h recording period,the analyzed data showed that there were significant differences in the sleep-wake transition frequency,slow-wave sleep(SWS)phase duration,rapid eye movement(REM)sleep phase duration,total SWS time,total REM time and total sleep time among the three groups(F=10.5,4.1,13.0,7.8,4.4,9.3,all P<0.05).The frequency of sleep-wake transitions in the pregabalin group((66.3±18.0)times)and the control group((87.8±14.1)times)were less than that in the model group((106.7±20.8)times)(both P<0.05).The duration of SWS phase((11.2±4.0)min)in pregabalin group was significantly longer than that in model group((5.9±1.8)min)(P<0.05),while that in model group was shorter than that in control group((7.7±1.2)min)(P<0.05).The duration of REM phase in the model group((1.9±0.4)min)was shorter than that in the control group((2.5±0.4)min)(P<0.05).There was no significant difference in the duration of REM phase between the pregabalin group and the model group(P>0.05).Within 7 h of observation,the total SWS time((296.5±37.1)min)and total sleep time((338.4±33.3)min)in pregabalin group were longer than those in model group((258.1±38.4)min,(288.9±41.0)min)(both P<0.05).The total REM time((30.4±11.1)min)and total sleep time((288.9±41.0)min)in the model group were significantly shorter than those in the control group((50.2±8.5)min,(339.0±19.6)min)(both P<0.05).Conclusion Pregabalin alone can reduce seizures and change the sleep structure disorder caused by epilepsy,which is mainly manifested in reducing the number of sleep-wake transitions,prolonging the duration of SWS,increasing sleep duration,increasing SWS and total sleep time and improving sleep quality.