摘要
目的:观察托吡酯、氟桂利嗪对大鼠海马快速电点燃模型-慢性颞叶癫痫模型的干预效果。方法:实验于2004-12在中山大学电生理实验室完成。选择8～10周成年雌性Wistar大鼠60只,右侧海马植入双极电极,随机数字表法分为对照组、单纯刺激组、氟桂利嗪组,托吡酯组和联合用药组,每组12只。对照组植入电极不予电刺激,单纯刺激组仅给予电刺激,氟桂利嗪组,托吡酯组和联合用药组刺激前90min分别给予40mg/kg氟桂利嗪、80mg/kg托吡酯及上述剂量两药联合灌胃。观察点燃率,点燃速度及异常脑电发放时间。经历全面痫性发作后,主动脉灌注法处死动物做右侧海马部尼氏体(标记神经元)和胶质纤维酸性蛋白(标记星形胶质细胞)染色并计数。对照组大鼠与其他组饲养相同天数后处死做病理检查。结果:对照组动物无死亡,单纯刺激组、氟桂利嗪组,托吡酯组和联合用药组分别有11,10,11,11只大鼠充分点燃并完成后续实验。成功率组间差异无显著性意义(P>0.05)。①单纯刺激组、氟桂利嗪组、托吡酯组和联合用药组首次全面点燃所需刺激次数分别为[(16.36±4.32)、(18.40±3.86)、(24.36±7.71)、(32.01±9.46)次],平均异常脑电发放时间分别为[(46.24±12.22)、(43.52±13.40)、(30.92±6.73)、(25.20±3.86)s],除单纯刺激组、氟桂利嗪组间差异无显著性意义(P>0.05),其余两两组间差异均有显著性意义(P<0.05);②对照组、单纯刺激组、氟桂利嗪组,托吡酯组和联合用药组动物右侧海马神经元计数均值分别为[(5958.5±167.5)、(4838.5±70.0)、(5159.0±175.5)、(5480.5±219.5)、(5547.0±321.0)个/mm2],星形胶质细胞计数均值分别为[(2162.5±173.0)、(3282.0±163.5)、(2872.0±163.0)、(2532.5±82.0)、(2502.5±137.5)个/mm2],除托吡酯组和联合用药组间差异无显著性意义(P>0.05),其余两两组间差异均有显著性意义(P<0.05)。结论:托吡酯对大鼠海马快速电点燃模型有明显抑制效果,氟桂利嗪作用不明显,联合用药时有一定的叠加作用。
AIM： To observe the intcrventional effect of topiramate and flunarizine in rapid hippocampal kindled and chronic temporal epilepsy rats.
METHODS： The experiment was carried out in the electrophysiological laboratory of Sun Yat-sen University in December 2004. Sixty adult female Wistar rats of 8-10 weeks were implanted with bipolar electrodes in the right hippocampus, and then divided into 5 groups according to the random number table method with 12 rats in each： control group, simple stimulation group, topiramate group, flunarizine group and topiramate＋ flunarizine group. Rats in the control group were only implanted with bipolar electrodes but not given electric stimulation, those in the simple stimulation group were only given electric stimulation, and those in the topiramate group, flunarizine group and topiramate＋flunarizine group were treated with topiramate （40 mg/kg）, flunarizine group （80 mg/kg） and topiramate （40 mg/kg） combined with flunarizine （80 mg/kg） at 90 minutes before stimulation respectively. The ratio of kindling, seizure behavior and the time of abnormal electroencephalogram （EEG） discharge were observed. After the overall attack of epilepsy, the rats were killed by means of aortic perfusion, the Nissl and glial fibriliary acidic protein staining were used to measure the amount of neurons and astrocytes in the right hippocampus tissue. The rats in the control group and simple stimulation group were killed after being raised and seizured for the same days, and then pathological examination, was performed.
RESULTS： No rat died in the control group. 11, 10, 11 and 11 rats were fully kindled and finished all the experiments in the simple stimulation group, topiramate group, flunarizine group and topiramate ＋flunarizine group respectively, and the successful rate had no significant difference among the groups （P 〉 0.05）. （1） In the simple stimulation group, topiramate group, flunarizine group and topiramate＋flunarizine group, the mean stimulation times needed to arouse first generalized seizure were （16.36±4.32）, （18.40±3.86）, （24.36±7.71）, （32.01±9.46） times, ,respectively; and the average times of abnormal EEG discharge （46.24 ±12.22）, （43.52±13.40）, （30.92±6.73）, （25.20±3.86） s, respectively. There were significant differences between every two groups （P 〈 0.05）, the simple stimulation group and flunarizine group （P〉 0.05）. （2） The right hippocampus neuron counting results in the control group, simple stimulation group, topiramate group, flunarizine group and topiramate＋ flunarizine group were （5 958.5± 167.5）, （4 838.5±70.0）, （5 159.0±175.5）, （5 4805±2195）, （5 547.0±321.0） cells/mm^2, respectively, and the astrocyte counting results were （2 162.5± 173.0）, （3 282.0± 163.5）, （2 872.0± 163.0）, （2 532.5±82.0）, （2 502.5±137.5） cells/mm^2, respectively. There were significant differences between every two groups （P 〈 0.05） except the topiramate group and topiramate＋flunarizine group （P 〉 0.05）.
CONCLUSION： Topiramate has obvious inhibitory effect on rapid hippocampal kindled rats; while flunarizine has little. The combined administration shows certain synergic effect.
出处
《中国临床康复》
CSCD
北大核心
2006年第14期108-110,共3页
Chinese Journal of Clinical Rehabilitation
基金
广东省自然科学基金重点项目资助(20013110)~~
