p38MAPK信号通路在癫痫大鼠中的激活及普瑞巴林的干预作用

Activation of p38MAPK in pentylenetetrazol-induced seizure rats and intervention effect of pregabalin

目的观察Y一氨基丁酸（GABA）受体阻滞剂普瑞巴林（PGB）对癫痫大鼠的干预作用及其作用机制。方法按随机数字表法将38只健康成年SD大鼠分为对照组，戊四氮（P＇rz）组，PGB低、中、高剂量组。按Racine分级方法观察癫痫大鼠行为学表现，同时描记脑电图变化；通过苏木素一伊红染色法观察海马神经元的形态学改变，采用免疫组织化学法检测海马组织p38MAPK的蛋白表达。结果与对照组比较，PTZ组大鼠癫痫发作级别明显增高，表现为Ⅳ一V级发作（P〈0．01），海马组织中p38MAPK的蛋白表达增强（P〈0．01）；与Prz组比较，PGB组大鼠癫痫发作级别明显降低，表现为I～Ⅲ级发作（P〈0．01），海马组织中p38MAPK的蛋白表达减弱（P〈O．05）；PGB组间比较，高、中剂量组大鼠癫痫发作级别较低剂量组降低（P〈0．05），海马组织中p38MAPK的蛋白表达较低剂量组减弱（P〈0．05）。结论p38MAPK通路在阿z诱导的癫痫大鼠海马中表达增强，GABA受体阻滞剂PGB对癫痫大鼠具有保护作用，其作用是通过间接下调p38MAPK的蛋白表达实现的。

Objective To explore activation of the p38MAPK signal pathway in pentylenetetrazol （PTZ）-induced seizure rats, and explore the intervention effect and mechanism of pregabalin（ PBG）, an inhibitor for γ-aminobutydc acid （GABA） receptors. Methods 38 adult Sprague-Dawley rats were randomly divided into 5 groups： the control group, the PTZ group and three doses of PBG-pretreated groups. After treatment with corresponding reagents, behavior, electrocorticogram and neuronal ultrastructural changes in the hippocampus were observed. Expression of p38MAPK in the hippoacampus of rats was determined by means of immunohistochemistry. Results Grade IV- V of seizure was detected in the PTZ group, while grade I -III of seizure in PBG-pretreated groups （ P 〈 0.05 ）. Compared with the control group, expression of p38MAPK was increased in the PTZ group （P 〈0.01 ）, while it was decreased in PBG-pretreated groups compared with the PTZ group （ P 〈 0.05 ）. Among PBG-pretreated groups, grade of seizure and expression of p38MAPK were lower in high and medium dose groups compared with the low dose group. Conclusions Expression of p38MAPK is significantly increased in the hippocampns of PTZ-induced seizure rats. PBG has a protective effect on PTZ-induced seizure rats by depressing expression of p38MAPK.