摘要
目的探究泽泻汤对高热量饮食介导的认知功能损害的影响及可能机制。方法将27只C57BL/J小鼠随机分成对照组、模型组和泽泻汤组,每组9只。模型组和泽泻汤组小鼠均采用高脂饲料喂养建立高热量饮食诱导认知功能损害小鼠模型,泽泻汤组在高脂饲料喂养的同时给予0.36 g/(kg·d)泽泻汤灌胃,对照组和模型组小鼠给予等体积生理盐水灌胃,持续8周。每周同一时间记录小鼠体质量;干预结束后,各组小鼠进行口服葡萄糖耐量测试、胰岛素耐量测试;利用莫利斯水迷宫实验、旷场实验、新物体识别实验、Y迷宫测试对小鼠进行认知行为学检测;核磁共振波谱检测小鼠左侧海马、下丘脑、皮层神经代谢物质N-乙酰天门冬氨酸(NAA)、胆碱(CHO)、乳酸(Lac)、肌酸(Cr)、脂质(Lip)、肌醇(mI)的表达;蛋白质免疫印迹法检测小鼠脑组织突触素(SYN)、突触体相关蛋白25(SNAP-25)、突触后致密蛋白95(PSD-95)、肿瘤坏死因子α(TNF-α)、核转录因子κB p65(NF-κB p65)及磷酸化核转录因子κB p65(p-NF-κB p65)的表达;尼氏染色检测海马神经元的形态变化。结果与对照组比较,模型组小鼠体质量、口服葡萄糖耐量测试血糖和胰岛素耐量测试血糖水平均升高;模型组小鼠在莫利斯水迷宫实验中第3天、第4天的移动总路程和逃避潜伏期增加、在平台区域停留时间和穿越平台次数减少,在旷场实验中模型组小鼠进入中心区域的次数、中心区域停留时间与总时间的比值、中心区域活动路程与总路程的比值显著减少,在新物体识别实验中模型组小鼠新物体识别频次和识别指数显著降低,Y迷宫测试中模型组小鼠自发交替率明显降低(P<0.05或P<0.01);模型组小鼠左侧海马、下丘脑和皮层的CHO/Cr、NAA/Cr明显降低,mI/Cr、Lac/Cr和Lip/Cr明显升高;脑组织中SYN/β-actin、SNAP-25/β-actin、PSD-95/β-actin值显著降低,p-NF-κB p65/NF-κB p65、TNF-α/β-ac
Objective To investigate the mechanism of Zexie Decoction(泽泻汤)in inhibiting neuroinflamma⁃tion and improving cognitive impairment mediated by high-calorie diet.Methods Twenty seven C57BL/J mice were randomly divided into control group(n=9),model group(n=9)and Zexie Decoction group(n=9).The mice in the model group and the Zexie Decoction group were fed with high-calorie diet to establish the model of cognitive im⁃pairment.Meanwhile,the mice in Zexie Decoction group were also fed with 0.36 g(/kg·d)Zexie Decoction,and the mice in the control group and model group were fed with the same volume of normal saline for 8 weeks.The body weight of mice was recorded at the same time every week;after intervention,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)commenced;the cognitive level of mice was detected by Morris water maze,open field test,new object recognition test and Y maze;magnetic resonance spectroscopy(MRS)was used to detect the expression of N-acetylaspartate(NAA),choline(CHO),lactic acid(Lac),creatine(Cr),lipid(Lip),and myoInositol(mI)in left hippocampus,hypothalamus and cortex.Western blotting was used to detect the expression of synaptophysin(SYN),synaptosome associated protein-25(SNAP-25),postsynaptic dense protein-95(PSD-95),tumor necrosis factor-α(TNF-α),nuclear factor kappa B(NF-κB p65)and its phosphorylated form(P-NF-B p65)in mouse brain;Nissl's staining was used to detect the morphological changes of hippocampal neurons.Results Com⁃pared with the control group,body mass,blood glucose in oral glucose tolerance test,and blood glucose in insulin tolerance test increased in the model group;in the Morris water maze experiment,the total distance travelled and es⁃cape latency of the model group mice increased,the time spent in the platform area and the number of times traversing the platform decreased on days 3 and 4;in the open-field experiment,the number of times the model group mice entered the central area,the ratio of the time in the central area to the total time,and th
作者
郑晓清
魏伟
李惠红
丁琳琳
薛偕华
ZHENG Xiaoqing;WEI Wei;LI Huihong;DING Linlin;XUE Xiehua(School of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,350122;Fujian University of Traditional Chinese Medicine Affiliated Rehabilitation Hospital/Key Laboratory of Cognitive Rehabilitation of Fujian Province;Rehabilitation Industry Research Institute,Fujian University of Traditional Chinese Medicine/Key Laboratory of Rehabilitation Technology of Fujian Province)
出处
《中医杂志》
CSCD
北大核心
2024年第4期395-403,共9页
Journal of Traditional Chinese Medicine
基金
国家自然科学基金(82274620)
福建省卫健委科技计划(2021zyyj69)
福建省自然科学基金(2021J01957)。
关键词
认知功能损害
高热量饮食
泽泻汤
突触蛋白
神经炎症
cognitive impairment
high-calorie diet
Zexie Decoction(泽泻汤)
synaptic proteins
neuroinflammation
