摘要
目的:研究脱氢表雄酮(dehydroepiandrosterone,DHEA)对血管性痴呆小鼠学习和记忆能力的改善作用及可能机制。方法:将小鼠随机分为假手术组、模型组及DHEA(20、40和60 mg/kg)组。采用夹闭小鼠双侧颈总动脉15 min再放开的方法,建立全脑缺血再灌注所致的血管性痴呆小鼠模型。通过Y迷宫和新物体辨别实验测试小鼠的学习和记忆能力;采用Western blot法检测小鼠海马组织神经元核抗原(NeuN)、突触小泡蛋白(SYP)和突触后致密蛋白95(PSD-95)的含量。结果:与假手术组相比,在Y迷宫和新物体辨别实验中,模型组小鼠出现显著的学习和记忆障碍,DHEA治疗能显著增加Y迷宫实验中小鼠自发交替反应率,同时还可显著提高小鼠新物体辨别实验的优先指数和辨别系数(P <0. 05),其中DHEA中剂量组效果最为显著(P <0. 01)。Western blot实验结果显示,模型组小鼠海马组织NeuN、SYP和PSD-95的表达水平与假手术组比显著降低(P <0. 05); DHEA组小鼠海马组织NeuN、SYP和PSD-95蛋白的表达较模型组显著增多(P <0. 05)。结论:DHEA具有提高血管性痴呆小鼠学习和记忆能力的作用,其机制可能与减少神经元的丢失和改善突触的可塑性有关。
AIM:To study the effects of dehydroepiandrosterone(DHEA)on the learning and memory of vascular dementia mice and its possible mechanisms.METHODS:The mice were randomly divided into sham group,model group and DHEA(20,40 and 60 mg/kg)group.The model of global cerebral ischemia was established by bilateral common carotid artery occlusion in the mice for 15 min.The learning and memory abilities of the mice were identified through Y maze and new object recognition test.The contents of neuronal nuclear antigen(NeuN),synaptophysin(SYP)and postsynaptic density protein-95(PSD-95)in the hippocampus were detected by Western blot.RESULTS:Compared with sham group,the model mice had significant learning and memory impairments in Y maze and new object recognition test.The rate of spontaneous alternating reaction in Y maze test was significantly increased and the preferential index and discrimination index for new objects were significantly improved in DHEA group(P<0.05).The effect in middle-dose DHEA group was the most significant(P<0.01).The results of Western blot showed that the expression of NeuN,SYP and PSD-95 in the hippocampus of the mice in model group was significantly lower than that in sham group(P<0.05).Compared with model group,the expression of NeuN,SYP and PSD-95 in the hippocampus of the mice in DHEA group was significantly increased(P<0.05).CONCLUSION:DHEA improves the abilities of learning and memory in vascular dementia mice.The mechanisms may be related to the reduction of neuronal loss and the improvement of synaptic plasticity.
作者
李静
白玉
张鹏
丁瑞
赵学梅
LI Jing;BAI Yu;ZHANG Peng;DING Rui;ZHAO Xue-mei(College of Pharmacy,Qiqihar Medical University,Qiqihar 161006,China;Clinical Pharmacology Department,Qiqihar Medical University,Qiqihar 161006,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第10期1905-1909,共5页
Chinese Journal of Pathophysiology
基金
黑龙江省大学生创新创业训练计划项目(No.201711230066)
