松果菊苷对糖尿病小鼠认知功能的改善作用的初步研究  

Preliminary research on the effect of echinacoside ameliorating cognitive impairment in diabetic mice

作　　者：覃方鳞 闫一鸣 杨柠溪 郝亚荣[1] QIN Fanglin;YAN Yiming;YANG Ningxi;HAO Yarong(Dept.of Geriatrics,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院老年病科,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2024年第11期1277-1284,1309,共9页Medical Journal of Wuhan University

基　　金：湖北省自然科学基金资助项目(编号:2016CFB673)。

摘　　要：目的探讨松果菊苷(ECH)对db/db小鼠认知功能障碍的改善作用及可能的机制。方法db/m小鼠为对照组,db/db小鼠分为模型组(db/db组)、ECH治疗组(db/db⁃ECH组)、二甲双胍(MET)治疗组(db/db⁃MET组)。db/m组和db/db组以0.9%氯化钠注射液[0.05 mL/(10 g·d)]灌胃,db/db⁃ECH组以松果菊苷(ECH)300 mg/(kg·d)灌胃,db/db⁃MET组以MET 200 mg/(kg·d)灌胃,连续干预14周。检测体质量、收缩压、舒张压、空腹血糖(FPG)、胰岛素抵抗指数(HOMA⁃IR)等指标;Morris水迷宫检测认知功能;ELISA检测血清肿瘤坏死因子α(TNF⁃α)、白细胞介素1β(IL⁃1β);免疫组化检测海马CA1区IL⁃1β、TNF⁃α;Western Blot检测TNF⁃α、IL⁃1β、Tau、P⁃Tau(S202/T205)、糖原合成酶激酶3β(GSK⁃3β)、P⁃GSK⁃3β(Ser9)、丝裂原激活蛋白激酶激酶(MEK)、P⁃MEK、细胞外信号调节激酶(ERK)、P⁃ERK表达情况。结果(1)一般情况:与db/db相比,db/db⁃ECH小鼠体质量、收缩压、空腹血糖、HOMA⁃IR均有所改善(P<0.05)。(2)Morris水迷宫:与db/db组相比,db/db⁃ECH小鼠逃避潜伏期缩短,目标象限停留时间延长(P<0.05),运动活跃。(3)TNF⁃α、IL⁃1β:与db/db组相比,db/db⁃ECH和db/db⁃MET组小鼠外周TNF⁃α表达降低(P<0.05),海马CA1区IL⁃1β、TNF⁃α阳性染色降低,海马细胞形态结构较为完整。(4)Western Blot:与db/db组相比,db/db⁃ECH组P⁃Tau(S202/T205)和Tau比值降低,P⁃GSK⁃3β(Ser9)和GSK⁃3β比值增加,P⁃MEK和MEK比值降低,P⁃ERK和ERK比值降低(P<0.05)。结论ECH能改善糖尿病小鼠炎症反应、神经元损伤,抑制Tau的过度磷酸化,改善糖尿病小鼠的空间学习和记忆能力,该功能可能与ECH抑制GSK⁃3β和MEK/ERK过度激活有关。Objective To investigate the effects and underlying mechanisms of echinacoside(ECH)on ameliorating cognitive impairment in diabetic mice.Methods The db/m mice were selected as the control group.The db/db mice were divided into the model group(db/db group),the ECH treatment group(db/db⁃ECH group),and the metformin(MET)treatment group(db/db⁃MET group).The db/m and db/db groups were gavaged with 0.9%sodium chloride injection(0.05 mL/[10 g·d]),the db/db⁃ECH group with ECH 300 mg/(kg·d),and the db/db⁃MET group with MET 200 mg/(kg·d),for a duration of 14 weeks.Measurements included body mass,systolic and diastolic blood pressure,fasting blood glucose(FPG),and homeostasis model assessment⁃insulin resistance(HOMA⁃IR).Morris water maze test was conducted to evaluate their cognitive function.Serum levels of tumor necrosis factorα(TNF⁃α)and interleukin 1β(IL⁃1β)were quantified using ELISA.Immunohistochemistry was performed to detect the expression levels of IL⁃1βand TNF⁃αin the hippocampal CA1 region;Western Blot analysis was conducted to assess the expression levels of IL⁃1β,TNF⁃α,Tau,phosphorylated Tau(P⁃Tau)at S202/T205,glycogen synthase kinase 3β(GSK⁃3β),phosphorylated GSK⁃3β(Ser9),mitogen⁃activated extracellular signal⁃regulated kinase(MEK),extracellular signal⁃regulated kinase(ERK).Results(1)General condition:The db/db⁃ECH group exhibited significant improvements in body mass,systolic blood pressure,fasting blood glucose,and HOMA⁃IR as compared with the db/db group(P<0.05).(2)Morris water maze:Compared with the db/db group,the db/db⁃ECH group showed shorter escape latency time and longer residence time in the target quadrant(P<0.05).(3)TNF⁃αand IL⁃β:Compared with the db/db group,the db/db⁃ECH and db/db⁃MET groups showed significantly reduced peripheral TNF⁃αlevels(P<0.05),diminished IL⁃1βand TNF⁃αimmunostaining in the hippocampal CA1 area,and preserved hippocampal cellular morphology and structural integrity.(4)Western Blot:Compared with the db

关 键 词：松果菊苷 糖尿病相关认知功能障碍 炎症反应 磷酸化TAU蛋白 

分 类 号：R749.1[医药卫生—神经病学与精神病学]