持续高盐饮食通过调节转录因子C/EBPβ促进阿尔兹海默病小鼠认知障碍  

Long-term High-salt Diets Aggravate Cognitive Impairment in Alzheimer's Disease Mice by Modulating the Transcription Factor C/EBPβ

作　　者：白桦 余杭 郑红云[1] BAI Hua;YU Hang;ZHENG Hong-yun(Department of Clinical Laboratory,Renmin Hospital of Wuhan University,Wuhan 430060,China;Department of Neurology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院检验医学中心检验科,武汉430060 [2]武汉大学人民医院检验医学中心神经内科,武汉430060

出　　处：《微循环学杂志》2024年第1期1-5,13,共6页Chinese Journal of Microcirculation

基　　金：国家自然科学基金(81100959)。

摘　　要：目的:探讨转录因子C/EBPβ参与高盐饮食加重阿尔茨海默病(AD)模型小鼠学习记忆损伤的机制。方法:实验小鼠分为APP/PS1-ND组、APP/PS1-HSD组、APP/PS1/C/EBPβ+/--ND组、APP/PS1/C/EBPβ+/--HSD组、APP/PS1/C/EBPβ-HDO-ND组、APP/PS1/C/EBPβ-HDO-HSD组,每组各15只,分别给予正常饮食或高盐饮食,通过新物体识别实验(NOR)、关联条件恐惧、暗示条件恐惧实验检测其学习记忆水平。荧光定量PCR检测海马脑区C/EBPβ mRNA水平,特定酶活试剂盒检测C/EBPβ活性。结果:APP/PS1-HSD组小鼠在NOR的T2实验中的区分指数与APP/PS1-ND组小鼠差异无统计学意义(P>0.05),APP/PS1-HSD组小鼠在NOR的T3实验中的区分指数、关联条件恐惧实验的僵直时间百分比以及暗示条件恐惧实验的僵直时间百分比均明显低于APP/PS1-ND组(P均<0.01)。APP/PS1/C/EBPβ+/--ND组与APP/PS1/C/EBPβ+/--HSD组小鼠在NOR的T2和T3实验中的区分指数以及关联条件恐惧实验的僵直时间百分比和暗示条件恐惧实验的僵直时间百分比的差异均无统计学意义(P>0.05)。APP/PS1/C/EBPβ-HDO-ND组与APP/PS1/C/EBPβ-HDO-HSD组小鼠在NOR的T2和T3实验中的区分指数、关联条件恐惧实验的僵直时间百分比以及暗示条件恐惧实验的僵直时间百分比的差异均无统计学意义(P>0.05)。与APP/PS1-ND组比较,APP/PS1-HSD组小鼠海马组织C/EBPβ mRNA水平和C/EBPβ活性均明显升高(P<0.01),APP/PS1小鼠海马组织C/EBPβ活性与其认知功能之间存在明显的负相关(r=-0.6215,P<0.05)。结论:C/EBPβ参与高盐饮食所介导的阿尔茨海默病的认知障碍,或可成为阿尔茨海默病的治疗新靶点。Objective:To investigate the mechanism of the role of transcription factor C/EBP-βin the learning and memory impairment of Alzheimer's disease(AD)model mice induced by high-salt diet.Method:Experimental mice were divided into APP/PS1-ND group,APP/PS1-HSD group,APP/PS1/C/EBPβ+/--ND group,APP/PS1/C/EBPβ+/--HSD group,APP/PS1/C/EBPβ-HDO-ND group,APP/PS1/C/EBPβ-HDO-HSD group,15 in each group,were given normal diet or high-salt diet,and their learning and memory levels were detected by novel object recognition test,contextural fear conditioning test and cued fear conditioning test.The mRNA level of CEBPB in hippocampal brain region was detected by fluorescence quantitative PCR,and the transcriptional activity of CEBPβwas detected by specific enzyme activity kit.Results:There was no significant difference between APP/PS1-HSD group and APP/PS1-ND group in NOR T2 test(P>0.05).The differentiation index of APP/PS1-HSD group in NOR T3 test,percentage of freezing time of contextural fear conditioning test and percentage of freezing time of cued fear conditioning test were significantly lower than those of APP/PS1-ND group(P<0.01).There were no significant differences between APP/PS1/C/EBPβ+/--ND group and APP/PS1/C/EBPβ+/--HSD group in NOR T2 and T3 tests,percentage of freezing time of contextural fear conditioning test and percentage of freezing time of cued fear conditioning test(P>0.05).There were no significant differences between APP/PS1/C/EBPβ-HDO-ND group and APP/PS1/C/EBPβ-HDO-HSD group in NOR T2 and T3 tests,percentage of freezing time of contextural fear conditioning test and percentage of freezing time of cued fear conditioning test(P>0.05).Compared with APP/PS1-ND group,C/EBPβmRNA level and C/EBPβactivity in hippocampus of APP/PS1-HSD group were significantly increased(P<0.01).There was a significant negative correlation between hippocampal C/EBPβactivity and cognitive function in APP/PS1 mice(r=-0.6215,P<0.05).Conclusion:C/EBPβis involved in cognitive impairment of Alzheimer's disease mediated by hi

关 键 词：高盐饮食 痴呆 C/EBPΒ 阿尔茨海默病 

分 类 号：R741[医药卫生—神经病学与精神病学]