北京大学学报（医学版）2016，Vol.48Issue(1)：154-159,6.DOI:10.3969/j.issn.1671-167X.2016.01.028
Keap1-tat小肽降低缺血后大鼠海马CA1区神经元氧化应激损伤和空间学习记忆缺陷
Keap1-tat peptide attenuates oxidative stress damage in hippocampal CA1 region and learning and memory deficits following global cerebral ischemia
摘要
Abstract
Objective:To design Keap1-tat peptide and explore its neuroprotective role on hipocampal CA1 neuron,as well as the effect on spacial learning and memory function following global cerebral ische-mia.Methods:Adult male Sprague Dawley (SD)rats were subjected to global cerebral ischemia (GCI) by four-vessel occlusion for 1 5 min and randomly divided into five groups:sham,sham+Keap1-tat,is-chemia/reperfusion (I/R),Keap1-tat peptide-and vehicle-administrated groups.For Keap1-tat or vehi-cle groups,the rats were treated with Keap1-tat (30,50,1 00 μg in 5 μL 0.9%saline)or the same vo-lume vehicle by intracerebroventricular injection (icv)30 min prior to ischemia.Cresyl violet staining was used to observe the surviving neurons and 4-hydroxy-2-noneal (4-HNE ) and 8-hydroxy-2′-deox-yguanosine (8-OHdG)immunostaining were used to detect the change of markers response to oxidative stress in hippocampal CA1 region.The spatial learning and memory function of the rats was evaluated using Morris water maze.Results:Compared with sham group,the number of surviving neurons in ische-mia-reperfusion and vehicle groups significantly decreased in the hippocampal CA1 region (P<0.05 ), while administration of Keap1-tat significantly decreased the damage following GCI (P<0.05),and the dose of 50 μg existed the most effective neuroprotective role.Furthermore,immunostaining intensity of 4-HNE and 8-OHdG,markers of oxidative stress damage attenuated by Keap1-tat peptide as compared with vehicle group in CA1 region.Of significant interest,the time of finding underwater platform in Keap1-tat group animals was significantly short,and after removing the platform,the probe time of Keap1-tat group animals in the original quadrant where the platform was significantly increased compared with that of vehi-cle and I/R group animals (P<0.05).Conclusion:Keap1-tat peptide can effectively attenuate neuro-nal damage in hippocampal CA1 region and improve learning and memory function,which might bedue to the attenuation of oxidative stress caused by GCI.关键词
脑缺血/再灌注损伤/氧化性应激/神经元/海马Key words
Brain ischemia/Reperfusion injury/Oxidative stress/Neurons/Hippocampus分类
医药卫生引用本文复制引用
涂静宜,朱莹,尚淑玲,张茜,唐慧,王瑞敏..Keap1-tat小肽降低缺血后大鼠海马CA1区神经元氧化应激损伤和空间学习记忆缺陷[J].北京大学学报（医学版）,2016,48(1):154-159,6.基金项目
河北省自然科学基金（C2014209277）和唐山市科技计划项目（121302071 a）资助Supported by Natural and Science Funds of Hebei Province （C2014209277）and Science and Technology Program of Tangshan City （）
