愈痫灵方对PTZ致痫鼠认知功能障碍与海马p-CREB、CaMK Ⅳ表达的影响

Effects of Yuxianling Decoction on the Cognitive Dysfunction and the Protein Expression of Hippocampus' p-CREB and CaMK Ⅳ in Epilepsy Rats caused by PTZ

目的分析愈痫灵方对海马磷酸化环磷腺苷应答元件结合蛋白(CREB)、钙调蛋白依赖性蛋白激酶Ⅳ(CaMK Ⅳ)的关系和表达变化,探讨愈痫灵方改善戊四氮(PTZ)致痫鼠认知功能障碍的影响。方法取健康雄性SD大鼠120只,从中随机选取10只作为正常对照组,其余大鼠用戊四氮造模,将符合模型标准的大鼠随机抽取60只分为愈痫灵组、拉莫三嗪组、丙戊酸钠组和模型组,每组15只。灌胃后用水迷宫实验测试大鼠的学习记忆能力,采用免疫组织化学方法检测p-CREB、Ca MK Ⅳ在海马体CA1区的表达变化。结果各组大鼠水迷宫实验潜伏期和总路程的学习记忆成绩比较有显著统计学意义(P<0.001):模型组与正常组比较,差异有显著统计学意义(P<0.001);拉莫三嗪组、愈痫灵组与模型组比较,差异有显著统计学意义(P<0.001)。愈痫灵方对致痫鼠海马CA1区P-CREB、CaMK Ⅳ表达的影响:各组之间表达的比较,差异有显著统计学意义(P<0.01);模型组与正常组比较,差异有显著统计学意义(P<0.01);愈痫灵组、拉莫三嗪组与模型组比较,差异有显著统计学意义(P<0.01)。结论愈痫灵方可以通过增强海马区p-CREB的水平,提高P-CREB的上游通路CaMK Ⅳ,改善致痫大鼠的学习记忆能力。

Objective To analyse the Yuxianling Decoction on the hippocampus＇ p-CREB and CaMK Ⅳ association and their expression change. To discuss the impacts of Yu Xian Ling Decoction on improving cognitive dysfunction of epilepsy rats caused by pentylenetetrazole（PTZ）. Methods 10 rats as the normal control group were randomly selected from120 healthy male SD rats, the rest of the rats were molding with PTZ. Conform to the model standards, the 60 rats were randomly divided into the Yuxianling（YXL） group, lamotrigine（LTG） group, valproate group and model group, 15 rats in each group. After lavage, the rats＇ learning and memory ability were tested by the Morris water maze. The p-CREB, CaMKⅣ expression changes in hippocampus CA1 area were detected by the immunohistochemical method. Results Compare of each group rats＇ water maze test of the incubation period and the total distance learning memory performance,the differences had significant statistical significance（P 0.001）; Compared with normal group, the model group had significant difference（P〈0.001）; The differences between the model group, LTG and YXL group were statistically significant（P〈0.001）. The influence of Yu Xian Ling Decoction on the expression changes of p-CREB and CaMKⅣ in hippocampus CA1 area of epilepsy rats caused by PTZ： the expression between each groups had statistical significance（P 0.01）; Compared with normal group, the model group had statistical significance（P〈0.01）; The YXL, LTG and model groups had statistical significance（P 0.01）. Conclusion Yuxianling Decoction could improve the epilepsy rats＇ cognitive dysfunction by enhancing the hippocampus p-CREB levels and increasing the CaMKⅣ of upstream pathways in p-CREB.