脂必泰对阿尔茨海默病小鼠糖脂代谢的影响  

Effect of Zhibitai tablets on glucose and lipid metabolism in Alzheimer’s disease mice

作　　者：周妮娜 谭佩珍[1] 邓明珠 王灿 ZHOU Ni-na;TAN Pei-zhen;DENG Ming-zhu;WANG Can(Department of Neurology,Hunan Provincial Brain Hospital,Changsha 410007,Hunan Province,China)

机构地区：[1]湖南省脑科医院神经内科,湖南长沙410007

出　　处：《中国临床药理学杂志》2021年第18期2481-2485,共5页The Chinese Journal of Clinical Pharmacology

基　　金：湖南省卫生健康委科研计划基金资助项目(20201642)。

摘　　要：目的探讨脂必泰对阿尔茨海默病(AD)小鼠糖脂代谢的影响。方法按照随机数字表法将APP^(swe)/PS1^(△E9)双转基因AD模型小鼠随机分为4组:模型组、多奈哌齐组(灌胃多奈哌齐3.25 mg·kg^(-1),qd)和高、低2个剂量脂必泰组(灌胃脂必泰60,30 mg·kg^(-1),qd)。将野生型C57BL/6J小鼠随机分为2组:正常组和脂必泰对照组,每组各10只,连续干预8周。模型组和正常组小鼠灌胃等量生理盐水。用Morris水迷宫法检测小鼠学习记忆能力,微型正电子发射断层成像和计算机断层扫描法检测脑葡萄糖代谢率,蛋白质印迹法检测磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(Akt)、糖原合成酶激酶-3β(GSK-3β)蛋白表达和磷酸化情况。结果正常组、脂必泰对照组、模型组、多奈哌齐组和高、低2个剂量脂必泰组小鼠穿台次数分别为(11.50±2.17),(11.80±2.10),(4.30±1.16),(8.10±2.33),(8.40±2.50),(7.10±2.51)次;这6组的大脑皮层组织18F-FDG摄取率分别为(3.28±0.29)%,(3.27±0.31)%,(2.08±0.22)%,(2.13±0.26)%,(2.89±0.25)%和(2.73±0.20)%ID·g^(-1);这6组的PI3K蛋白含量分别为0.87±0.11,0.88±0.12,0.45±0.07,0.50±0.08,0.76±0.08和0.68±0.07;这6组的p-Akt/Akt比值分别为0.63±0.07,0.65±0.06,0.42±0.05,0.48±0.06,0.57±0.05和0.51±0.06;这6组的p-GSK-3β/GSK-3β比值分别为0.72±0.08,0.76±0.11,0.43±0.05,0.45±0.06,0.64±2.50和0.65±0.09。模型组与正常组比较,上述指标均降低(均P<0.05),表明造模成功。而各脂必泰组与模型组比较,上述各指标均升高(均P<0.05);而脂必泰对照组和正常组比较,上述各指标无明显变化(均P>0.05),表明脂必泰对野生型小鼠无影响。结论脂必泰通过激活PI3K/Akt/GSK-3β信号通路,改善AD模型小鼠学习记忆能力,减轻脑组织神经元损伤,并改善糖脂代谢紊乱。Objective To study the effect of Zhibitai tablets on glucose and lipid metabolism in Alzheimer’s disease(AD)mice.Methods APP^(swe)/PS1^(△E9)double transgenic AD mice were divided into 4 groups according to random number table:Model group,Donepezil group(Donepezil 3.25 mg·kg^(-1),ig,qd),Zhibitai-L and Zhibitai-H groups(Zhibitai 30,60 mg·kg^(-1),ig,qd).Wild type C57BL/6J mice were divided into 2 groups:Control group and Zhibitai-WT group(Zhibitai 60 mg·kg^(-1),ig,qd)with 10 mice in each group.All mice were treated for 8 weeks continuously.Normal group and model group were treated with normal saline(ig,qd).The learning,memory function of mice were evaluated by Morris water maze test.Micro-positron emission computed tomography/computed tomography(micro PET/CT)was used to measure cerebral glucose metabolism rate of mice.Expression levels(gray value)of the phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),glycogen synthese kinase-3β(GSK-3β)proteins and phosphorylation were detected by Western blot.Results The times of crossing plateform in normal group,Zhibitai-WT group,model group,donepezil group and two zhibitai-H,-L groups were respectively(11.50±2.17),(11.80±2.10),(4.30±1.16),(8.10±2.33),(8.40±2.50),(7.10±2.51)times;18F-FDG uptake rates in the 6 groups were respectively(3.28±0.29)%,(3.27±0.31)%,(2.08±0.22)%,(2.13±0.26)%,(2.89±0.25)%and(2.73±0.20)%ID·g^(-1);the expressions of PI3K protein in the 6 groups were respectively 0.87±0.11,0.88±0.12,0.45±0.07,0.50±0.08,0.76±0.08 and 0.68±0.07;p-Akt/Akt ratio in the 6 groups were respectively 0.63±0.07,0.65±0.06,0.42±0.05,0.48±0.06,0.57±0.05 and0.51±0.06;p-GSK-3β/GSK-3βratio in the 6 groups were respectively 0.72±0.08,0.76±0.11,0.43±0.05,0.45±0.06,0.64±2.50 and 0.65±0.09.Comparison between model group and normal group,the above indexes were all lower,the difference was significant(all P<0.05),which indicated that the model group was successful.Comparison between Zhibitai group and model group,all the above indexes were increa

关 键 词：脂必泰 APP^(swe)/PS1^(△E9)双转基因小鼠 阿尔茨海默病 糖脂代谢 神经元凋亡 磷脂酰肌醇-3激酶/蛋白激酶B/糖原合成酶激酶-3β信号通路 

分 类 号：R97[医药卫生—药品]