反复惊厥和大剂量抗痫药对大鼠海马pCREB的影响及草果知母汤的干预作用

目的探讨反复惊厥发作和大剂量苯妥英钠造成大鼠认知障碍模型中磷酸化cAMP反应元件结合蛋白（pCREB）的变化,并观察草果知母汤的作用。方法利用戊四唑（PTZ）诱导癫痫模型,再通过每日PTZ点燃癫痫和大剂量苯妥英钠注射造成大鼠认知功能障碍,然后分为每日发作模型组（A）、每日发作草果知母汤治疗组（B）、每日发作尼莫地平治疗组（C）、大剂量苯妥英钠组（D）、苯妥英钠草果知母汤治疗组（E）、苯妥英钠尼莫地平治疗组（F）,用免疫组化和Western blotting方法检测大鼠海马组织pCREB的变化。结果B、C组大鼠pCREB表达均有明显提高,与A组比较,差异有显著性;E、F组大鼠海马部位的pCREB的变化与D组比较差异亦有显著性。结论草果知母汤改善癫痫每日发作和苯妥英钠所致大鼠的认知障碍可能是通过提高pCREB表达而发挥作用的。

Influence of Repeated Seizures and Large Dosage Anti-epileptic Drug on Phosphorylated cAMP Response Element Binding Protein in Rat's Hippocampus and Effect of Caoguo Zhimu Decoction on It

Objective To study the influence of repeated seizures and anti-epileptic drug on phosphorylated cAMP response element binding protein (pCREB) in rat model of cognitive impairment, and the effect of Caoguo Zhimu Decoction (CZD) on it. Methods On the basis of epileptic model induced by pentylenetetrazol (PTZ), cognitive impairment model was induced by kindling epilepsy with PTZ everyday, which were then divided into the model-1 group, the CZD-1 group, the nimodipine-1 group, and those by injecting large dosage phenytoin sodium were divided into the model-2 group, the CZD-2 group and the nimodipine-2 group. Changes of pCREB protein in rat's hippocampus were detected using immunohistochemistry and Western blotting assay. Results The expression of pCREB was higher in the CZD-1 and nimodipine-1 group than in the model group, while it was significantly different in the CZD-2 and nimodipine-2 groups than in the model-2 group. Conclusion CZD could relieve the cognitive dysfunction in the epileptic model rats induced by everyday PTZ kindling or by dilantin through increasing the pCREB expression.