戊四氮点燃大鼠癫痫发作和癫痫形成过程中海马5-HT水平的变化

目的：研究戊四氮（PTZ）点燃大鼠癫痫形成过程中行为、脑电及海马5-羟色胺（5-HT）水平的变化。方法：对大鼠腹腔注射PTZ35mg／（kg·d），观察行为变化，在不同时间点（第7、14、21、28天），进行脑电记录，微透析取海马组织间液，活体观察24只自由活动大鼠在点燃过程和诱发发作前后脑电、海马5-HT及其代谢产物5-羟吲哚乙酸（5-HIAA）水平及其5-HT转化率（5-HIAA／5-HT）的变化。结果：开始PTZ注射后，发作潜伏期逐日缩短，发作程度逐日加重，点燃时间在10～14d。在制模过程中有一只鼠死亡。海马脑电随着发作的加重而出现癫痫波潜伏期缩短，癫痫波量增加，发作间期出现自发放电。点燃早期（第7天），发作间期大鼠的海马5-HT水平略有升高，随着点燃时间延长，5-HT水平逐渐降低，在点燃后（第14天）维持点燃（第21、28天）5-HT水平持续下降，与点燃前5-HT水平比较，差异无显著意义（P〉0．05）；5-HT转化率在点燃过程变化差异无统计学意义；5-HIAA水平在点燃时期和维持点燃时期呈逐步降低，点燃期、维持点燃期与对照组比较差异有显著意义（P〈0．05）。结论：PTZ点燃大鼠癫痼形成过程中，在点燃前，发作间期的海马5-HT水平呈阶段性升高，点燃后，发作间期的海马5-HT水平逐渐降低；点燃后，发作间期的海马5-HT水平明显低于正常水平；随着维持点燃时间延长，发作间期的海马5一HT水平呈进行性下降。

The variance of 5-HT levels of hippocampus in rats with PTZ-induced kindling epilepsy

Objective：To investigate the variance of behavior, EEG and 5-HT levels in rats with pentylenetrazol（PTZ）-induced kindling epilepsy. Methods： The microdialysis probe and hippocampus electrode were placed into the dorsal hippocampus of rats on 7^th d, 14^thd, 21th d, 28^th d of inducing （35 mg/ （kg · d） PTZ IP）. Three hours after seizures dialysate was collected and concentrations of extracellular 5- HT, and its metabolite 5-hydroxyindolacetic acid （5-HIAA） were assessed by HPLC-ECD. Hippocampus EEG at the same time in free-running rats was recorded. Results.. From the day of inducing on the latency of seizures was shortened gradually and the degree of seizures was more and more aggravated. In 10-14 days all rats were kindled, one died during inducing. With the aggravation of seizure, EEG show gradually aggravate epileptic discharge. The latency of epileptic discharge was shortened. Spontaneous discharge appeared during seizures. In kindling periods, the concentrations of 5HT, 5-HIAA in rats dorsal hippocampus were a litter increased and 5-HT turnover （5-HIAA/5-HT） decreased , but not have significant difference. In advanced stage （28^thd） of kindling, Concentrations of 5-HT and 5-HIAA decreased significantly compared with the controls （ P〈0.05）, 5-HT turnover did not significantly decrease as compared with the controls. After rats were kindled, maintenance efficient kindling （PTZ 20 mg/（kg ·d） IP） can keep on degrading 5-HT concentrations. Concentrations of 5-HT and 5 HIAA on the 7^thd and 14^thd have significantly different from those on 21^thd and 28^thd （P〈0.05）. Conclusions： During epileptogenesis development, hippocampus 5-HT levels increase in early stage of kindling,and decrease gradually in advanced stage of kindling. With the time of kindling passing, levels of hippocampus 5-HT lower continuously in progress. Hippocampus 5-HT levels significantly lower down to normal ones after kindling, and it exist persistently.