藏红花素介导DKK3调控GSK-3β/β-catenin通路对阿尔兹海默症大鼠的认知改善作用  

Improvement effect of crocin on cognitive impairment of Alzheimer's disease rats through DKK3 regulation of GSK-3β/β-Catenin pathway

作　　者：杨晓佳[1] 江萌[1] 吴敏[1] 张伊黎 吕兰[1] 吴嫄芬 王鑫昱[1] 刘立权[1] YANG Xiaojia;JIANG Meng;WU Min;ZHANG Yili;LV Lan;WU Yuanfen;WANG Xinyu;LIU Liquan(Hangzhou Hospital of Traditional Chinese Medicine,Hangzhou 310007,Zhejiang,China)

机构地区：[1]杭州市中医院,浙江杭州310007

出　　处：《中国临床药理学与治疗学》2023年第5期489-497,共9页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省中医药科技计划项目(2022ZB236)。

摘　　要：目的:探讨藏红花素(crocin)对阿尔兹海默症(Alzheimer’s disease,AD)小鼠认知能力的改善作用及机制。方法:SD大鼠海马区注射Aβ25-35建立AD模型,随机分为AD组、AD+L、M、H-crocin组(10、20、40 mg/kg)和AD+donepezil组(1 mg/kg盐酸多奈哌齐),腹腔注射治疗4周,另设置Sham组。采用避暗实验、水迷宫实验评估大鼠学习、记忆能力,ELISA测定大鼠血清Aβ含量,HE染色和Tunel染色确定大鼠海马区内病理改变及神经元细胞凋亡,免疫组化测定大鼠海马区Brdu、Dcx、NeuN表达,Western blot测定大鼠脑组织Aβ、DKK3、β-catenin、p-GSK-3β/GSK-3β、Caspase-3、Bax、Bcl-2蛋白表达。结果:与Sham组相比,AD组大鼠的学习、记忆能力下降,血清Aβ含量升高,且海马区的病理改变严重,神经元细胞凋亡增加,Brdu、Dcx、NeuN含量降低,Aβ、DKK3、pGSK-3β/GSK-3β、Caspase-3、Bax蛋白表达升高,β-catenin、Bcl-2蛋白表达降低(P<0.01)。与AD组相比,给予不同剂量crocin和donepezil治疗后,AD大鼠学习、记忆能力提高,血清Aβ含量降低,海马区的病理改变减轻,神经元细胞凋亡减少,Brdu、Dcx、NeuN含量升高,Aβ、DKK3、p-GSK-3β/GSK-3β、Caspase-3、Bax蛋白表达升高,β-catenin、Bcl-2蛋白表达降低(P<0.05),crocin的剂量依赖效应显著。结论:crocin通过减少神经元细胞凋亡,介导DKK3调控GSK-3β/β-catenin通路来改善AD大鼠认知损伤。AIM:To explore the improvement ef-fect and mechanism of crocin on cognitive impairm-rnt of Alzheimer's disease(AD)rats.METHODS:The hippocampus of SD rats were injected with Aβ25-35 to establish AD model,then rats were ran-domly divided into AD group,AD+low,medium,high dose of crocin groups(10,20,40 mg/kg)and AD+donepezil group(1 mg/kg),intraperitoneal in-jection treatment for 4 weeks,set sham group.Dark avoidance test and water maze test were used to evaluate the learning and memory abilities of rats,ELISA was used to detect serum Aβcon-tent,HE staining and Tunel staining were used to determine pathological changes and neuronal apoptosis of hippocampus of rats,immunohisto-chemistry was used to detect the expression of Br-du,Dcx and NeuN in hippocampus of rats,and Western blot was used to detect the protein ex-pression of Aβ,DKK3,β-catenin,p-GSK-3β/GSK-3β,Caspase-3,Bax,Bcl-2 in hippocampus of rats.RE-SULTS:Compared to sham group,the learning and memory abilities of AD group rats were decreased,serum Aβcontent increased,the pathological change in hippocampus was serious,neuronal apoptosis was increased,the expression of Brdu,Dcx,NeuN were decreased,the protein expression of Aβ,DKK3,p-GSK-3β/GSK-3β,Caspase-3,Bax were increased,protein expression ofβ-catenin,Bcl-2 were decreased(P<0.01).Compared to AD group,after the treatment of doses of crocin and donepe-zil,the learning and memory abilities of AD rats were improved,serum Aβcontent were increased,and the pathological change in hippocampus were alleviated,neuronal apoptosis were reduced,the expression of Brdu,Dcx,NeuN were decreased,the protein expression of Aβ,DKK3,p-GSK-3β/GSK-3β,Caspase-3,Bax were decreased,the pro-tein expression ofβ-catenin,Bcl-2 were increased,notely,dose-dependent effect of crocin was signifi-cant.CONCLUSION:Crocin reduced neuronal apoptosis and mediated DKK3 to regulate GSK-3β/β-catenin pathway to improve the cognitive impair-ment of AD rats.

关 键 词：藏红花素 阿尔兹海默症 神经细胞凋亡 DKK3 GSK-3β/β-catenin通路 

分 类 号：R965.2[医药卫生—药理学]