中国药理学与毒理学杂志2025，Vol.39Issue(11)：801-812,12.DOI:10.3867/j.issn.1000-3002.2025.08542
六味地黄苷糖及其糖苷通过调控脑内O-GlcNAc修饰改善小鼠记忆再巩固损伤
Liuwei Dihuang-active fraction combination and its active compo-nent glycoside improve memory reconsolidation impairment by regulating brain O-GlcNAc modification
摘要
Abstract
OBJECTIVE To investigate the effects of Liuwei Dihuang-active fraction combination(LW-AFC)and its active component glycoside(LWD-b)on memory reconsolidation and their relation-ship with O-linked β-N-acetylglucosamine(O-GlcNAc)modification.METHODS ① Six-month-old senescence-accelerated mouse prone 8(SAMP8)mice were divided into three groups:SAMP8 group,SAMP8+LW-AFC group and SAMP8+LWD-b group.Senescence-accelerated mouse resistant 1(SAMR1)mice served as the control group.The SAMP8+LW-AFC group and SAMP8+LWD-b group were given LW-AFC 1.6 g·kg-1 and LWD-b 0.216 g·kg-1 ig for 60 days,respectively,while the SAMR1 group and SAMP8 group were ig given the same volume of deionized water.② Male C57BL/6J mice were divided into four groups:control group,exogenous corticosterone(CORT)group,CORT+LW-AFC group,and CORT+LW-AFC+6-diazo-5-oxo-L-norleucine(DON)group.The CORT group was given CORT 25 mg·kg-1 sc for 15 consecutive days;CORT+LW-AFC group was given LW-AFC ig for 30 consecutive days,and CORT at 25 mg·kg-1 sc continuously from the 15th day;CORT+LW-AFC+DON group was given LW-AFC ig for 30 consecutive days,and CORT at 25 mg·kg-1 sc and DON at 600 μg·kg-1 ip continuously from the 15th day.The control group was given an equal volume of deionized water ig per day.③ C57BL/6J mice were divided into the control group,CORT group,CORT+LWD-b group,and CORT+LWD-b+DON group.The drug was administered at the same time and in the same order asin②except that LW-AFC 1.6 g·kg-1 was replaced by LWD-b 0.216 g·kg-1.In three experiments,the modified novel object recognition test(retrieval-enhancement paradigm)and conditional fear test(retrieval-extinction paradigm)were used to evaluate memory reconsolidation.ELISA and Western blotting were performed to detect hippocampus O-GlcNAc levels.Pearson correlation analysis was used to explore the correlations between memory reconsolidation performance(preference index of the novel object and freezing time after retrieval)and O-GlcNAc levels.RESULTS ①Compared with the SAMR1 group,the SAMP8 group showed a significantly decreased preference index for the novel object,prolonged freezing time,and reduced hippocampal O-GlcNAc levels.Compared with the SAMP8 group,SAMP8+LW-AFC and SAMP8+LWD-b groups showed a significantly increased preference index for the novel object,decreased freezing time,and elevated hippocampal O-GlcNAc levels.Pearson analysis revealed a positive correlation between the novel object preference index and O-GlcNAc levels,and significantly negative correlations between context/cue freezing time and O-GIcNAc levels.②Compared with the control group,the CORT group showed a significantly decreased preference index for the novel object,prolonged freezing time,and reduced hippocampal O-GlcNAc levels.Compared with the CORT group,the CORT+LW-AFC group showed a significantly increased preference index for the novel object,decreased freezing time,and elevated hippocampal O-GlcNAc levels.Compared with the CORT+LW-AFC group,the CORT+LW-AFC+DON group showed a significantly decreased preference index for the novel object,prolonged freezing time,and reduced hippocampal O-GlcNAc levels.Pearson analysis revealed a positive correlation between the novel object preference index and O-GlcNAc levels,but a significantly negative correlation between context/cue freezing time and O-GIcNAc levels.③ Compared with the control group,the CORT group showed a significantly decreased preference index for the novel object,prolonged freezing time,and reduced hippocampal O-GlcNAc levels.Compared with the CORT group,the CORT+LWD-b group showed a significantly increased preference index for the novel object,decreased freezing time,and elevated hippocampal O-GlcNAc levels.Compared with the CORT+LWD-b group,the CORT+LWD-b+DON group showed a significantly decreased preference index for the novel object,prolonged freezing time,and reduced hippocampal O-GlcNAc levels.Pearson analysis revealed a positive correlation between the novel object preference index and O-GlcNAc levels,but a significantly negative correlations between context/cue freezing time and O-GIcNAc levels.CONCLU-SION LW-AFC and LWD-b can significantly ameliorate memory reconsolidation impairment induced by aging and stress in mice,and the mechanism may be associated with upregulation of O-GlcNAc modifi-cation levels in the hippocampus of mice.关键词
六味地黄苷糖/LWD-b/记忆再巩固/O-GlcNAc修饰/SAMP8/外源性皮质酮模型小鼠Key words
LW-AFC/LWD-b/memory reconsolidation/O-GlcNAc modification/SAMP8/exogenous corticosterone model mice分类
医药卫生引用本文复制引用
杨贺禧,王晨冉,夏梦婷,王健辉,周文霞..六味地黄苷糖及其糖苷通过调控脑内O-GlcNAc修饰改善小鼠记忆再巩固损伤[J].中国药理学与毒理学杂志,2025,39(11):801-812,12.基金项目
国家重点研发计划(2022YFC3502003) （2022YFC3502003）
国家重点研发计划(2022YFC3500304) （2022YFC3500304）
国家自然科学基金(82174006) （82174006）
北京市自然科学基金(7222292) National Key R&D Program of China(2022YFC3502003) （7222292）
National Key R&D Program of China(2022YFC3500304) （2022YFC3500304）
National Natural Science Foundation of China(82174006) （82174006）
and Beijing Municipal Natural Science Foundation(7222292) （7222292）
