匹鲁卡品癫痫鼠脑室注射5-氮胞苷导致ERK表达增加.docVIP

  匹鲁卡品癫痫鼠脑室注射 5-氮胞苷导致 ERK 表达增加# 肖飞，胡以达，李杰，杜超* 5 10 15 20 25 30 35 40 45 （重庆医科大学附属第一医院神经内科，重庆，400016） 摘要：目的：细胞外调节蛋白激酶(extracellular regulated protein kinases,ERKs)在癫痫发病机 制中起重要作用，但是其调控机制尚不完全清楚。我们的前期研究发现 RasGRF1 在难治性 癫痫脑组织中减低，其表达受甲基化调控。我们拟通过干预 RasGRF1 甲基化研究其对 ERK 表达的影响。方法：建立匹鲁卡品癫痫大鼠模型，分为 5-氮胞苷干预组、生理盐水假手术 组和单纯模型组（每组 18 只），在建模成功后 1 天、3 天和 7 天时取脑组织颞叶及海马， 采用免疫印迹法检测其中 RasGRF1 及 ERK 表达，并进行相关性分析。结果：成功建立模型， 在各时间点 RasGRF1 表达逐渐减低，但生理盐水假手术组和单纯模型组减低较 5-氮胞苷干 预组显著，差异具有统计学意义(P0.05)。ERK 在各时间点中表达逐渐升高，但 5-氮胞苷干 预组升高较另两组更明显，差异具有统计学意义(P0.05)。结论：给予甲基化抑制剂 5-氮胞 苷干预 RasGRF1 合成，癫痫大鼠脑组织中 ERK 表达进一步增加，提示 RasGRF1 对于 ERK 的正向调节作用。RasGRF1 在癫痫脑组织中表达减低可能是机体在癫痫这种疾病状态下的 一种负反馈机制。 关键词：癫痫；RasGRF1；甲基化；细胞外调节蛋白激酶 中图分类号：R742.1 Intracerebroventricular injection of 5- azacytidine in Pilocarpine induced epilepsy rat leads to increased expression of ERK Xiao Fei, Hu Yida, Li Jie, Du Chao (Neurology Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016) Abstract: Purpose: Extracellular regulated protein kinases (ERKs) play an important role in the pathogenesis of epilepsy, but its regulatory mechanism is not fully understood yet. Our preliminary study showed that reduction of RasGRF1 in brain tissue of patients with refractory epilepsy, and it is regulated by methylation. We intend to intervene of RasGRF1 methylation and study its effects on the expression of ERK. Methods: Pilocarpine induced epileptic rat models were established, and they were divided into three groups: 5- azacytidine treated group, saline sham operation group and simple model group (n = 18). Temporal lobe and hippocampus were obtained 1, 2 and 7 day after successfully modeling. Western blot was used to detect the expression of RasGRF1 and ERK, and correlation analysis was made. Results: Models was successfully established. Expression of RasGRF1 gradually reduced at different time point as time goes on, but saline sham operation group and simple model groups were lower than 5- azacytidine intervention grou