耐药性颞叶癫痫大鼠认知和焦虑及抑郁行为学变化及意义

Changes of cognition,anxiety and depression in rats with drug-resistant temporal lobe epilepsy

目的探究耐药性颞叶癫痫大鼠在认知、焦虑、抑郁等方面的行为学变化及意义。方法选取雄性SD大鼠80只,随机抽取6只为正常对照组,其余大鼠采用腹腔注射氯化锂-毛果芸香碱制备癫痫模型,2周后出现自发性反复癫痫发作(spontaneously recurrent seizures,SRS)的大鼠给予苯巴比妥、苯妥英钠干预筛选出药物敏感大鼠和耐药大鼠,各选6只。采用24 h视频监控记录大鼠SRS的次数、等级及持续时间。采用Morris水迷宫实验、旷场实验、强迫游泳实验和糖水偏好实验观察各组大鼠认知、焦虑、抑郁方面的行为表现。结果(1)耐药组癫痫发作次数、发作等级及持续时间较药敏组明显增加(P<0.05)。(2)耐药组大鼠强迫游泳不动时间较药敏组和正常对照组增加,糖水偏好率降低(均P<0.05)。(3)耐药组大鼠在旷场实验中的总运动距离较正常对照组增加,站立次数减少,理毛次数多(均P<0.05)。与药敏组比较,耐药组总运动距离更长,站立次数更少(P<0.05)。各组间进入中心区域次数比较无统计学差异。(4)耐药组大鼠Morris水迷宫实验中4 d的平均逃避潜伏期较正常对照组均延长(P<0.05),且第2~4天其逃避潜伏期长于药敏组(P<0.05)。与正常对照组比较,耐药组穿越原平台区域次数、进入目标象限次数减少(P<0.05),目标象限停留时间短(P<0.05)。结论氯化锂-毛果芸香碱诱导的慢性颞叶癫痫大鼠存在认知功能减退及焦虑、抑郁情绪障碍,且耐药性癫痫大鼠的行为学表现异常较药敏组更加明显。耐药性癫痫可能会加重认知、焦虑及抑郁障碍。

Objective To explore the changes of cognition,anxiety and depression in rats with drug-resistant temporal lobe epilepsy.Methods 80 male Sprague Dawley rats were prepared,and 6 were randomly selected as a normal control group.The remaining rats were injected intraperitoneally with lithium chloride and pilocarpine to prepare epilepsy models.After 2 weeks,rats with spontaneously recurrent seizures(SRS)were treated with phenobarbital and phenytoin to screen out drug-sensitive epilepsy rats and drug-resistant epilepsy rats,6 rats were selected in each group.All the rats were continuously monitored by video,and the frequency,Racine degree and duration time of SRS were recorded.Morris water maze test,open field test,forced swimming test and sugar water preference test were performed,and the changes of cognition,anxiety and depression were observed.Results(1)The frequency of SRS,Racine degree and duration time of SRS of the drug-resistant group were significantly higher than the drug-sensitive group(P<0.05).(2)Compared with the drug-sensitive group and the normal control group,the immobility time of the drug-resistant group increased(P<0.01),and the sucrose preference rate decreased in the drug-resistant group(P<0.05).(3)In the open field test,compared with the normal control group,the total distance of the drug-resistant group increased,the number of standings decreased and the number of grooming increased(P<0.05).Compared with the drug-sensitive group,the total distance increased and the number of standings decreased in the drug-resistant group(P<0.05);there was no significant difference in the number of entering the central area.(4)The average escape latency of 4 days in the Morris water maze test of the drug-resistant group was longer than that of the normal control group(P<0.05),and the 2-4 days were also significantly longer than that of the drug-sensitive group(P<0.05).The number of crossing the original platform area,entering the target quadrant and the residence time in the target quadrant were reduced in the drug-resistant group compared with the normal control group(P<0.05).Conclusions Rats with chronic temporal lobe epilepsy induced by lithium chloride-pilocarpine have cognitive decline and anxiety depression disorders.The behavioral abnormalities of drug-resistant epilepsy rats are more obvious than those of the drug-sensitive group.Drug-resistant epilepsy may aggravate cognition impairment,anxiety,and depression in rats.