奥拉西坦及异构体神经保护和抗痴呆的药效学研究  

Pharmacodynamic study of chiral oxiracetam on neuroprotection and anti-dementia

作　　者：王玲[1] 徐少峰[1] 冯楠[1] 王伟平 王晓良[1] WANG Ling;XU Shao-feng;FENG Nan;WANG Wei-ping;WANG Xiao-liang(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院,北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2022年第9期2738-2742,共5页Acta Pharmaceutica Sinica

基　　金：新药作用机制研究与药效评价北京市重点实验室(BZ0150).

摘　　要：比较奥拉西坦及其手性异构体对神经损伤和动物记忆障碍模型的药效。体外利用谷氨酸和钙离子建立原代神经元损伤模型,评价奥拉西坦异构体对原代神经元的保护作用。体内利用手术结扎大鼠的双侧颈总动脉,分为假手术组、模型组、加兰他敏3 mg‧kg^(-1)组、消旋奥拉西坦(30、100和200 mg‧kg^(-1))、左旋奥拉西坦(30、100和200 mg‧kg^(-1))和右旋奥拉西坦200 mg‧kg^(-1)组。本研究中的动物实验是按照北京协和医学院福利伦理审查委员会的伦理指导方针进行的。利用跳台和Morris水迷宫实验评价奥拉西坦异构体对大鼠脑低灌注诱导的认知功能障碍的改善作用。研究结果显示,左旋、右旋和消旋奥拉西坦对不同诱导剂所致的原代神经元损伤均有一定的保护作用,其中左旋和消旋体的作用较强。在双侧颈总动脉结扎诱导的痴呆大鼠模型上,左旋、消旋和右旋奥拉西坦均显示改善脑低灌注诱导的大鼠学习和记忆缺失。综上所述,奥拉西坦对原代神经元损伤及动物痴呆模型均有一定的治疗作用,左旋奥拉西坦效果最明显。To compare the neuroprotective and anti-dementia pharmacological effects of chiral oxiracetam,glutamate and calcium ions were used to establish neuronal injury models in vitro,and the protective effects of chiral oxiracetam on primary neurons were assayed by MTT.Permanent bilateral common carotid artery occlusion(2-VO)-induced rats were randomly divided into sham group,model group,galantamine 3 mg‧kg^(-1)group,oxiracetam groups(30,100 and 200 mg‧kg^(-1)),S-oxiracetam groups(30,100 and 200 mg‧kg^(-1))and R-oxiracetam 200 mg‧kg^(-1)group.The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College.Morris water maze and stepdown test were applied to evaluate the cognitive dysfunction induced by cerebral hypoperfusion in rats.Oxiracetam,S-oxiracetam and R-oxiracetam exerted protective effects on primary neuronal damage caused by various stimuli,and oxiracetam and S-oxiracetam showed better neuro-protective effects.Morris water maze and step-down results showed that oxiracetam,S-oxiracetam and R-oxiracetam improved the cognition of 2-VO rats.In summary,Soxiracetam exerted a better neuro-protective effect than oxiracetam and R-oxiracetam.

关 键 词：奥拉西坦 光学异构体 脑保护 学习记忆 血管性痴呆 

分 类 号：R966[医药卫生—药理学]