摘要
目的研究西酞普兰(提高脑内5-羟色胺水平)、利血平(耗竭5-羟色胺)对癫癎形成过程的影响,探讨大脑5-羟色胺(5-HT)水平变化在癫癎形成的作用。方法大鼠随机分为对照组、戊四氮组、西酞普兰组、利血平组;用西酞普兰和利血平干预后,再用戊四氮点燃形成慢性癫癎,在点燃过程,进行海马脑电记录和微透析取样,在体观察48只自由活动大鼠行为、脑电和发作间期5-羟色胺能神经递质的变化。结果 (1)在点燃早期,西酞普兰组发作潜伏期延长,发作程度轻和点燃时间延长,发作死亡率低,与戊四氮组比较差异有显著性(P<0.05);点燃后,西酞普兰组诱发发作潜伏期、发作程度的变化与戊四氮组比较无统计学意义。点燃初期,西酞普兰组大鼠的海马5-HT水平升高,5-HT转化率(5-HIAA/5-HT)降低,与对照组和戊四氮组比较有显著性差异(P<0.05);点燃后,西酞普兰组5-HT水平降低,与PTZ组比较无统计学意义;与对照组比较有显著性差异(P<0.05);西酞普兰组5-HIAA水平在点燃过程逐渐降低与对照组比较,差异有统计学意义(P<0.01),与戊四氮组比较差异无统计学意义;点燃后,5-HT转化率(5-HIAA/5-HT)变化与戊四氮组和对照组比较,无统计学意义。(2)在点燃初期,利血平组发作潜伏期缩短,发作程度重,点燃时间缩短,发作死亡率高,与对照组、戊四氮组比较,差异有统计学意义,(P<0.05);点燃后,发作情况与戊四氮组比较,有统计学意义。点燃初期,利血平组5-HT水平降低与戊四氮组和对照组比较,差异有统计学意义(P<0.05),点燃后,利血平组5-HT水平逐渐下降与对照组比较差异有统计学意义(P<0.05),和PTZ组差异无统计学意义;点燃过程中,5-HIAA水平,利血平组呈逐日下降趋势,与对照组比较差异有统计学意义(P<0.01),与PTZ组差异无统计学意义;点燃期间和维持点燃期利血平组5-HT转化率(5-HIAA/5-HT)变化,与对照组和戊四氮组比较,差异无统计学意义。结论提高大脑5-HT水平,戊四氮点燃大鼠癫癎形成所需点燃时间显著延长;在戊四氮点燃大鼠早期,提高大脑5-HT水平,癫癎发作程度明显减轻;但提高大脑5-HT水平,未能最终阻断戊四氮点燃的癫癎形成;癫癎形成后,提高大脑5-HT水平未能抑制癫癎发作。降低大脑5-HT水平,戊四氮点燃大鼠癫癎形成所需点燃时间显著缩短;在戊四氮点燃大鼠期间,降低大脑5-HT水平,癫癎发作程度明显加重;降低大脑5-HT水平,可加速戊四氮点燃癫癎形成。
Objective To investigate the effect of serotonin（5-HT） levels on the pentylenetetrazol（PTZ）-induced kindling in rats.Methods Forty eight rats were divided into 4 groups in random（control group,PTZ group,CTP group,RSP group）.Citalopram（CTP）,which increased 5-HT levels,and reserpine（RSP）,which decreased 5-HT levels,were administrated by gavage one week before intraperitoneal injection of PTZ.At d7,d14,d21,d28 of PTZ kindling,hippocampus EEG was recorded.The dialysates were collected at seizure intervals（3h after seizures）;5-HT and 5-HIAA levels were assessed by HPLC-ECD in 48 free-running rats.Results During kindling,in CTP group,seizures degree was lighter than that in PTZ group,latent period of induced seizures and time to be kindled were longer than that of PTZ group（P0.05）;there were no significant differences in these parameters after kindling.During kindling,in CTP group,latent period of epileptic discharge recorded by EEG,was longer than that of PTZ group（P0.05）.During kindling（d7）,in CTP group 5-HT levels were increased and 5-HT turnover（5-HIAA/5-HT） decreased compared with that of PTZ group（P0.05）.After kindling（d28）,in CTP group 5-HT levels and 5-HIAA levels were decreased compare with that of PTZ（P0.01）.During kindling（d7）,in RSP group,seizures degree was severer,latent period of seizures was shorter,time to be kindled was shorter than those of PTZ group（P0.05）.During kindling,in RSP group,EEG latent period of epileptic discharge was shorter than that of PTZ group（P0.05）.During kindling,in RSP group,5-HT levels were decreased and 5-HT turnover（5-HIAA/5-HT） increased compared with that of control and PTZ group（P0.05）.After kindled（d28）,in RSP group as well as PTZ group 5-HT levels and 5-HIAA levels were decreased compared with that of control group（P0.01）.Conclusion Increase of brain 5-HT levels result in significant prolongation of latent period of PTZ-induced kindling in rats;during period of kindling,increase of 5-HT levels may lessen PTZ-induced seizures degree.
出处
《同济大学学报（医学版）》
CAS
2012年第6期58-63,共6页
Journal of Tongji University(Medical Science)
基金
国家自然科学基金项目(30570634)
关键词
戊四氮
癫癎
微透析
海马
5-羟色胺
西酞普兰
利血平
pentylenetrazol
epilepsy
microdialysis
hippocampus
serotonin
citalopram
reserpine
