人参总皂苷对后肢悬吊大鼠奖励性操作式条件反射能力的保护作用  

Protective effects of ginseng total saponins on reward-directed operant conditioning in hindlimb suspension rats

作　　者：董李晋川 陈颖[1] 胡秦[2] 鲍余 潘瑞乐[3] 曾桂荣 彭博[1] 刘新民[3,5] 石哲[6] DONG Lijinchuan;CHEN Ying;HU Qin;BAO Yu;PAN Ruile;ZENG Guirong;PENG Bo;LIU Xinmin;SHI Zhe(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;The Faculty of Environment and Life,Beijing University of Technology,Beijing 100124,China;Institute of Medicinal Plant Development,Peking Union Medical College&Chinese Academy of Medical Sciences,Beijing 100193,China;Hunan Key Laboratory of Pharmacodynamics and Safety Evaluation of New Drugs&Hunan Provincial Research Center for Safety Evaluation of Drugs,Changsha,Hunan 410331,China;Institute of Drug Discovery Technology,Ningbo University,Ningbo,Zhejiang 315000,China;Division of Stem Cell Regulation and Application&Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]北京工业大学环境与生命学院,北京100124 [3]中国医学科学院北京协和医学院药用植物研究所,北京100193 [4]新药药效与安全性评价湖南省重点实验室&湖南省药物安全性评价研究中心,湖南长沙410331 [5]宁波大学新药技术研究院,浙江宁波315000 [6]湖南中医药大学药学院湘产大宗药材品质评价湖南省重点实验室&干细胞中药调控与应用实验室,湖南长沙410208

出　　处：《Digital Chinese Medicine》2023年第4期416-425,共10页数字中医药（英文）

基　　金：Space Medical Experiment Project of Chinese Manned Space Program (HYZHXM05003);Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences (CI2021A04905)。

摘　　要：目的 本研究旨在探讨人参总皂苷(GTSs)对持续暴露于微重力环境导致的宇航员认知障碍的治疗作用。方法 按完成奖赏条件反射适应任务的时间,将50只无特定病原体(SPF)雄性Wistar大鼠随机分为对照组、后肢悬吊(HLS)组、石杉碱甲(HLS-Hup A 0.1 mg/kg)组、 GTSs低剂量(HLS-GTSs100 mg/kg)组和GTSs高剂量(HLS-GTSs 200 mg/kg)组。除对照组外,其余各组大鼠后肢悬吊并给予药物治疗(第20–58天),进行奖赏反射测试,并对大鼠的海马进行尼氏体染色和蛋白质印迹检测。结果 造模后,与对照组比较,HLS组大鼠按压杠杆次数减少,完成奖赏条件反射任务Ⅰ的时间延长(P <0.05),而HLS-GTSs 100和200 mg/kg组大鼠上述指标无明显变化(P> 0.05)。奖赏操作条件反射Ⅱ实验中,与对照组相比,HLS组大鼠按压杠杆次数明显减少(P <0.05),触摸鼻腔次数明显减少(P <0.01);与HLS组大鼠比较,HLS-GTSs 100 mg/kg组大鼠杠杆按压次数和鼻触次数均明显增加(P <0.05),HLS-GTSs200 mg/kg组完成时间显著缩短,杠杆按压次数显著增加(P <0.05)。视觉信号辨别实验中,与对照组大鼠相比,HLS组大鼠视觉信号辨别测试指标降低(P <0.01),HLS-GTSs 100和200 mg/kg组大鼠视觉信号辨别能力明显升高(P <0.01)。奖赏消退实验中,与对照组相比,HLS组大鼠的杠杆按压次数显著增加(P <0.01);与HLS组相比,HLS-GTSs 100和HLS-GTSs 200 mg/kg组大鼠的杠杆按压次数显著降低(P <0.05)。HLS组大鼠N-甲基-D-天冬氨酸受体1 (NR1)和磷酸化N-甲基-D-天冬氨酸受体2B(p-NR2B)蛋白表达明显降低(分别为P <0.01和P <0.05),而NR2B蛋白表达无明显变化(P> 0.05)。GTSs可上调p-NR2B的表达水平(P <0.01)。结论 GTSs通过调节NR1/NR2B磷酸化通路改善大鼠对复杂操作的学习记忆能力。Objective To explore the therapeutic effects of ginseng total saponins(GTSs)on cognitive impairments in astronauts caused by prolonged exposure to microgravity environment.Methods Fifty specific pathogen-free(SPF)male Wistar rats were randomized into control,hindlimb suspension(HLS),Huperzine A(HLS-Hup A 0.1 mg/kg),low-dose GTSs(HLS-GTSs 100 mg/kg),and high-dose GTSs(HLS-GTSs 200 mg/kg)groups,based on the completion time of reward-directed conditioning tasks.Except for rats in the control group,the others were subjected to HLS and treated with drugs(day 20–58),received reflex test under the condition of rewarding,and underwent Nissl body staining and Western blot detection on hippocampal.Results After modeling,rats in HLS group exhibited a reduction in the number of lever presses and an increase in the completion time of the reward-directed operant conditioning taskⅠ(P<0.05)when compared with the control group,which were not substantially altered in the HLS-GTSs 100 and 200 mg/kg groups(P>0.05).In the reward-directed operant conditioning taskⅡ,the HLS group rats demonstrated a marked decrease in the number of lever presses(P<0.05)and nose pokes(P<0.01)when compared with the control group rats;the HLS-GTSs 100 mg/kg showed a significant increase in the number of lever presses and nose pokes(P<0.05),while the HLS-GTSs 200 mg/kg demonstrated a significant reduction in completion time and an elevation in the number of lever presses(P<0.05)when compared with the HLS group rats.In visual signal discrimination task,compared with the control group rats,the HLS group rats showed decrease in the indexes of the visual signal discrimination(P<0.01),while HLS-GTSs 100 and 200 mg/kg groups exhibited manifest increase in it(P<0.01).In reward extinction experiment,the number of lever presses in HLS rats significantly increased when compared with the control group(P<0.01);compared with the HLS group,HLS-GTSs 100 and 200 mg/kg groups demonstrated a marked descrease(P<0.05).The expressions of N-methyl-D-aspartic acid receptor

关 键 词：人参总皂苷 模拟失重 学习记忆 奖励奖赏条件反射 N-甲基-D-天冬氨酸受体 

分 类 号：R285.5[医药卫生—中药学]