化痰祛瘀汤调控Wnt/β-catenin信号通路对血管性痴呆大鼠认知功能的影响  

Effects of Huatan Quyu Decoction on cognitive function of vascular dementia rats by regulating Wnt/β-catenin signal pathway

作　　者：刘梦媛 方永军[1] 胡亚莉[1] 韦鹏方 乔森 田与乾 赵鑫雅 刘惠 孔静渊 朱晓娜 Liu Mengyuan;Fang Yongjun;Hu Yali;Wei Pengfang;Qiao Sen;Tian Yuqian;Zhao Xinya;Liu Hui;Kong Jingyuan;Zhu Xiaona(First Clinical College of Shaanxi University of Chinese Medicine,Xianyang 712000,China;Second Department of Encephalopathy,Hospital Affiliated to Shaanxi University of Chinese Medicine,Xianyang 712000,China)

机构地区：[1]陕西中医药大学第一临床医学院,咸阳712000 [2]陕西中医药大学附属医院脑病医院二病区,咸阳712000

出　　处：《国际中医中药杂志》2024年第10期1310-1315,共6页International Journal of Traditional Chinese Medicine

基　　金：陕西省科技厅重点研发项目(2023-YBSF-435)。

摘　　要：目的基于Wnt/β-连环蛋白(β-catenin)信号通路观察化痰祛瘀汤对血管性痴呆大鼠β-catenin、GSK-3β蛋白表达及对认知功能相关蛋白抗心磷脂抗体(ACA)和β-淀粉样蛋白(Aβ)表达的影响。方法将96只雄性SD大鼠按随机数字表法分为空白组、模型组、多奈哌齐组及化痰祛瘀汤低、中、高剂量组,每组16只。除空白组外,其余各组采用改良2-VO法制备血管性痴呆大鼠模型,中药低、中、高剂量组分别灌胃化痰祛瘀汤6.1、12.1、24.2 g/kg,西药组灌胃盐酸多奈哌齐0.5 mg/kg,空白组及模型组灌胃等量生理盐水,连续28 d。给药第1、7、14、28天进行Morris水迷宫实验评估大鼠学习记忆能力,ELISA法测定大鼠血清ACA、Aβ水平,Western blot法测定大鼠海马组织β-catenin、GSK-3β蛋白表达。结果与模型组比较,给药7、14 d化痰祛瘀汤高剂量组、多奈哌齐组逃避潜伏期缩短(P<0.05),给药1、28 d化痰祛瘀汤高剂量组大鼠穿台次数增多(P<0.05)。与模型组比较,给药后第1、7、14、28天,多奈哌齐组及化痰祛瘀汤中、高剂量组大鼠血清ACA水平降低(P<0.05);给药后第7、14、28天多奈哌齐组及化痰祛瘀汤中、高剂量组大鼠血清Aβ水平降低(P<0.05);给药后第14、28天,化痰祛瘀汤低剂量组大鼠血清ACA、Aβ水平降低(P<0.05)。与模型组比较,多奈哌齐组及化痰祛瘀汤中、高剂量组大鼠海马组织β-catenin蛋白表达升高(P<0.05),多奈哌齐组及化痰祛瘀汤低、中、高剂量组大鼠海马组织中GSK-3β表达降低(P<0.01)。结论化痰祛瘀汤可激活Wnt/β-catenin信号通路,上调海马组织中β-catenin蛋白表达,抑制GSK-3β蛋白表达,降低血清ACA、Aβ水平,改善血管性痴呆大鼠认知功能。Objective To observe the effects of Huatan Quyu Decoction on the protein expressions ofβ-catenin and GSK-3βand the expression of anticardiolipin antibody andβ-amyloid protein related to cognitive function in rats with vascular dementia based on Wnt/β-catenin signal pathway.Methods A total of 96 male SD rats were divided into blank group,model group,Donepezil hydrochloride group and Huatan Quyu Decoction low-,midium-,high-dosage group according to random number table method,with 16 rats in each group.Except for the blank group,the rat model of vascular dementia was prepared by modified 2-VO method.Huatan Quyu Decoction low-,medium-and high-dosage groups were administrated with Huatan Quyu Decoction 6.1,12.1 and 24.2 g/kg,respectively;the Western medicine group was administrated with Donepezil hydrochloride 0.5 mg/kg;the blank group and the model group were administrated with the same amount of normal saline for 28 consecutive days.On the 1st,7th,14th and 28th day after administration,the learning and memory ability of rats was evaluated by Morris water maze test,the levels of ACA and Aβin serum were measured by enzyme linked immunosorbent assay(ELISA),and the expressions ofβ-catenin and GSK-3βproteins related to Wnt/β-catenin signal pathway in hippocampus were measured by Western blot.Results Compared with model group,the escape latency was shortened in the Huatan Quyu Decoction high-dosage group and Donepezil group on 7 and 14 days of administration(P<0.05),and the times of crossing the platform increased in Huatan Quyu Decoction high-dosage group on 1 and 28 days of administration(P<0.05).Compared with model group,the serum ACA level in Donepezil group,Huatan Quyu Decoction medium-and high-dosage groups decreased at day 1,7,14 and 28 after administration(P<0.05).The serum Aβlevel in Donepezil group,Huatan Quyu Decoction medium-and high-dosage groups decreased at 7,14 and 28 days after administration(P<0.05);On the 14th and 28th days after administration,the levels of ACA and Aβin TCM low-dosage group d

关 键 词：痴呆 血管性 认知障碍 WNT信号通路 抗心磷脂抗体 Β-淀粉样蛋白 化痰祛瘀汤 大鼠 

分 类 号：R285.5[医药卫生—中药学]