硫丙咪胺对戊四氮致痈幼鼠海马GFAP、c—fos表达和学习认知的影响

目的：观察硫丙咪胺（Thi）对戊四氮（PTZ）致痫幼大鼠海马胶质原纤维酸性蛋白（GFAP）、c-fos表达及学习认知的影响。方法：发育期SD幼鼠40只随机分为对照组、PTZ致瘸组、TM 30mg·kg^-1干预组和Thi15mg·kg^-1干预组（均n=10）。观察各组大鼠瘸样行为，水迷宫实验观察学习认知能力、免疫组化检测海马GFAP和c-fos的变化。结果：对照组无痫样发作，阿z致痫组有重度发作，Thi30mg·kg^-1干预组有轻度发作（P〈0．05）；水迷宫实验中，PTZ致痫组寻找平台潜伏时间延长和通过平台次数减少，Thi30和15mg·kg^-1干预组寻找平台潜伏时间明显缩短，通过平台次数增加明显，差异有统计学意义（P〈0．05）；PTZ致痫组GFAP和c-fos表达明显强于Thi干预组，差异有统计学意义（P〈0．05），其中Tiff30与15mg·kg^-1干预组相比差异也有统计学意义（P〈o．05）；GFAP和c—fos免疫组化表达与大鼠空间学习记忆能力呈正相关。结论：Thi可能通过抑制PTZ致瘸幼大鼠海马GFAP、c—fos表达，减轻癫痫发作程度，提高其学习认知能力。

Influence of Thioperamide on Learning and Memory and Expressions of GFAP and c-fos in Hippocampus of Epileptic Rats During Growth by Pentylenetrazole

Aim ： To observe the influence of thioperamide on the learning and memory and expressions of GFAP and c-fos in hippocampus of epileptic rats during growth by pentylenetrazole. These findings suggest that histamine H3 receptor antagonists might be useful in the treatment of cognitive impairment in epilepsy, and to explore the role of thioperamide in the epileptogenesis and development processes. Methods： Forty developing Sprague-Dawley （SD）mice were randomly divided into control group （n=10）, PTZ group （n=10） and thioperamide intervening group [（30 mg·kg^-1）high dose n=10, （15 mg·kg^-1）low dose n=10]. The behavior and Morris water maze test of rats were observed. The expressions of GFAP and c-fos in hippocampus were detected with immunohistochemistry. Results： The control group showed no seizure activity. Severe seizure activity was observed in the PTZ group, but slight seizure activity appeared in the thioperamide intervening group of high dose（P〈0.05）. The Morris water maze tests showed that the learning and memory ability of group PTZ were worsen than those of the control, the thioperamide intervening group was better than those in the others. The expressions of GFAP and c-fos were stronger in the PTZ group than those of the control group and thioperamide intervening group（P〈0.05）. The Morris water maze tests were negatively correlated to the lever expressions of GFAP and c-fos. Condusion： Thioperamide, by inhibiting the functions and proliferation of glial cells and expressions of c-fos in hippocampus, can alleviate the seizure activity. Cognitive function impairment could be improved by thioperamide intervening in PTZ kindling rats ,which suggests that thioperamide may be an ideal anticonvulsant in preventing and treating epilepsy.