吡仑帕奈对癫痫大鼠ERK/CREB/BDNF信号通路及认知功能的影响  

Effects of perampanel on ERK/CREB/BDNF signaling pathway and cognitive function in epileptic rats

作　　者：尤华琴[1] 张延英[1] 吴俊晓[1] 刘前[2] YOU Hua-Qin;ZHANG Yan-Ying;WU Jun-Xiao(Nanyang Medical High Vocational School,Nanyang 473000,Henan,China)

机构地区：[1]南阳医学高等专科学校,河南南阳473000 [2]南阳医学高等专科学校第一附属医院神经内科

出　　处：《中国老年学杂志》2022年第15期3715-3720,共6页Chinese Journal of Gerontology

基　　金：国家自然科学基金青年科学基金项目(81603266);河南省医学科技攻关计划项目(2019020319)。

摘　　要：目的观察吡仑帕奈(PER)对癫痫大鼠认知功能的影响,并初步探讨其作用机制。方法将采用戊四氮(PTZ)诱导制备成功的癫痫模型Wistar大鼠随机分为模型组、PER低、中、高剂量组,每组12只,PER低剂量组、PER中剂量组和PER高剂量组分别给予0.3、1.0和3.0 mg/kg PER灌胃处理10 w,1次/d;另选取12只正常大鼠设为对照组,对照组和模型组给予等量生理盐水灌胃处理。评估各组癫痫发作情况;莫里斯水迷宫(MWM)法检测各组大鼠认知功能变化情况;酶联免疫吸附试验检测各组大脑皮层组织丙二醛(MDA)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-10水平和超氧化物歧化酶(SOD)活性;尼氏染色法检测各组大鼠大脑皮层神经元细胞状态;Western印迹法检测各组大脑皮层组织细胞外信号调节蛋白激酶(ERK)、磷酸化(p)-ERK、cAMP反应元件结合蛋白(CREB)、p-CREB和脑源性神经营养因子(BDNF)蛋白表达。结果对照组尼氏小体丰富且分布均匀,大脑皮层神经元排列整齐;模型组大脑皮层神经元胞质染色不足,神经元细胞排列紊乱;经PER治疗后,各组大脑皮层组织神经元形态得以恢复。与对照组相比,模型组癫痫发作频率、癫痫持续时间、Racine分级、逃避潜伏期、目标象限停留时间、大脑皮层组织MDA、TNF-α水平显著增加(P<0.05),穿越原平台位置的次数、大脑皮层组织IL-10水平、SOD活性、p-ERK/ERK、p-CREB/CREB和BDNF蛋白表达显著降低(P<0.05)。与模型组相比,PER低剂量组、PER中剂量组和PER高剂量组癫痫发作频率、癫痫持续时间、Racine分级、逃避潜伏期、目标象限停留时间、大脑皮层组织MDA、TNF-α水平依次明显降低(P<0.05),穿越原平台位置的次数、大脑皮层组织IL-10水平、SOD活性、p-ERK/ERK、p-CREB/CREB和BDNF蛋白表达依次明显升高(P<0.05)。结论PER能够改善癫痫大鼠认知功能障碍,可能与促进大鼠大脑皮层组织ERK/CREB/BDNF通路活化,降低�Objective To observe the effect of perampanel(PER)on cognitive function in epileptic rats and explore its mechanism.Methods The Wistar rats of epilepsy model successfully prepared by pentylenetetrazol(PTZ)induction were randomly divided into model group,PER low-,medium-and high-dose groups,12 in each group.PER low-,medium-and high-dose group were given 0.3,1.0 and 3.0 mg/kg PER treated by gavage for 10 weeks,1 times/day.Another 12 normal rats were selected as control group,the control and the model groups were gavaged with the same amount of normal saline.The epileptic seizures were evaluated;Morris water maze(MWM)was used to detect the changes of cognitive function;the levels of malondialdehyde(MDA),tumor necrosis factor(TNF)-α,interleukin(IL)-10 and the activity of superoxide dismutase(SOD)in cerebral cortex tissue of rats were detected by enzyme-linked immunosorbent assay;Nissl staining was used to detect the status of neurons in cerebral cortex;Western blot analysis was used to detect the protein expressions of extracellular signal-regulated protein kinase(ERK),phosphorylation ERK(p-ERK),cAMP-response element binding protein(CREB),phosphorylation CREB(p-CREB)and brain-derived neurotrophic factor(BDNF)of cerebral cortex tissue of rats in each group.Results In the control group,Nissl bodies were abundant and evenly distributed,and the neurons in the cerebral cortex were arranged orderly;in the model group,the cytoplasmic staining of neurons in the cerebral cortex was insufficient,and the arrangement of neurons cells was disordered;after PER treatment,the morphology of neurons in cerebral cortex of rats in each group was restored.Compared with the control group,the epilepsy seizure frequency,epilepsy duration,Racine grade,escape latency,target quadrant dwell time,MDA and TNF-αlevels in cerebral cortex tissue of rats in the model group were significantly increased(P<0.05),times of crossing the original platform location,IL-10 level,SOD activity,p-ERK/ERK,p-CREB/CREB and BDNF protein expressions of cerebral cort

关 键 词：吡仑帕奈 癫痫 认知功能障碍 细胞外信号调节蛋白激酶 CAMP反应元件结合蛋白 脑源性神经营养因子 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]