醒脑静注射液改善老龄大鼠全麻后认知功能障碍及其机制研究  

Effect of Xingnaojing injection on cognitive impairment following anesthesia in aged rats

作　　者：信红亚[1] 石镇港 王平 吴莉峰 张妙红 厉巧 袁湘中 徐永兴 曾贵荣 万继峰 XIN Hong-ya;SHI Zhen-gang;WANG Ping;WU Li-feng;ZHANG Miao-hong;LI Qiao;YUAN Xiang-zhong;XU Yong-xing;ZENG Gui-rong;WAN Ji-feng(Xiangya Hospital,Central South University,Changsha 410002,China;Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs&Hunan Provincial Research Center for Safety Evaluation of Drugs,Changsha 410331,China;National Key Laboratory Breeding Base of Hunan Province Traditional Chinese Medicine Powder and Innovative Medicine,Changsha 410208,China;Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine,Beijing 100700,China)

机构地区：[1]中南大学湘雅医院,长沙410002 [2]湖南省药物安全评价研究中心&新药药效与安全性评价湖南省重点实验室,长沙410331 [3]湖南省中药粉体与创新药物省部共建国家重点实验室培育基地,长沙410208 [4]北京中医药大学东直门医院,北京100700

出　　处：《中国新药杂志》2020年第12期1405-1411,共7页Chinese Journal of New Drugs

基　　金：湖南省重点研发项目(2018SK2115)。

摘　　要：目的:研究醒脑静注射液改善老龄大鼠麻醉后认知功能障碍作用。方法:雄性老龄大鼠采用七氟烷连续麻醉4 h建立麻醉后认知障碍模型。记录首次给药后动物苏醒时间;分别在给药3和7 d后进行新物体识别和Morris水迷宫检测;采用酶联免疫(Elisa)试剂盒检测脑脊液中多巴胺(dopamine,DA)和谷氨酸(glutamate,Glu)水平;脑组织HE染色后观察病理组织改变;采用WB检测海马组织N-甲基-D-天冬氨酸受体(N-methyl-D-aspartic acid receptor,NMDAR1)表达。结果:单次静脉(iv)给予醒脑静注射液能明显减少大鼠七氟烷连续麻醉4 h后的苏醒时间,连续3或7 d给予醒脑静注射液(1.8,3.6和5.4 mL·kg-1)能显著改善全麻后老龄大鼠学习能力,降低给药3 d脑脊液中Glu水平,改善海马组织病理学改变,增加海马组织NMDAR1的表达。结论:醒脑静注射液能明显改善全麻后老龄大鼠认知障碍,其作用与增加海马组织NMDAR1表达有关。Objective:To study the effect of Xingnaojing injection on cognitive impairment after sevoflurane general anesthesia in aged rats.Methods:The cognitive impairment model was induced by continuous sevoflurane anesthesia for 4 h in male aged rats.Wake time after the first drug treatment,and both new object recognition and Morris water maze test of animals after 3 or 7 d drug treatment were determined,respectively;dopamine(DA)and glutamate(Glu)levels in cerebrospinal fluid were determined by Elisa kits,pathological changes were observed in brain tissue slices with HE staining,and the protein expression of N-methyl-D-aspartic acid receptor(NMDAR1)in hippocampus was detected by Western blot.Results:Single dose Xingnaojing injection treatment(1.8,3.6 and 5.4 mL·kg-1,iv)could significantly reduce wake time after 4 h of sevoflurane anesthesia,3 or 7 d treatment with Xingnaojing injection(1.8,3.6 and 5.4 mL·kg-1,qd,iv)could significantly increase in learning ability and reduce the level of Glu in cerebrospinal fluid,and the pathological damages of hippocampal improved as well.The protein expression of NMDAR1 in the hippocampus significantly increased by continuous sevoflurane anesthesia for 4 h in male aged rats.Conclusion:Xingnaojing injection could significantly improve the cognitive impairment following general anesthesia in male aged rats,and its effect maybe related to the increase of NMDAR1 protein expression in hippocampus.

关 键 词：醒脑静注射液 认知障碍 麻醉 

分 类 号：R964[医药卫生—药理学]