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梓醇-川芎嗪方对SAMP8小鼠认知功能的改善作用及机制

Effect of Catalpol-Tetramethylpyrazine Prescription on Cognitive Function of SAMP8 Mice

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目的:探讨梓醇-川芎嗪方(CT)对快速老化(SAMP8)小鼠认知功能的改善作用及其机制.方法:将50只14周龄SAMP8小鼠随机分为模型(Model)组、梓醇-川芎嗪方低剂量(CT-L)组、中剂量(CT-M)组、高剂量(CT-H)组、盐酸多奈哌齐组(DH组),10只14周龄快速衰老模型对照(SAMR1)小鼠作为对照(Control)组.Control组及Model组均以生理盐水灌胃,各用药组以相应药物灌胃,每日1次,连续8周.采用自主活动实验、筑巢行为实验、新物体辨别实验、Morris水迷宫实验等行为学观察.行为学观察后,检测各组小鼠海马组织超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、β-淀粉样蛋白(Aβ)1-42、p-Tau、核因子-κB(NF-κB)p65、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)及活性氧(ROS)水平,检测各组小鼠血清NF-κB p65、NLRP3、TNF-α、IL-1β及ROS含量.结果:与Model组比较,DH、CT-M、CT-H组小鼠自主活动次数、筑巢行为评分升高、对新物体辨别时间增加、新旧物体辨别时间比值升高、逃避潜伏期明显缩短、跨平台次数和目标象限停留时间增加(P<0.05).与CT-L组比较,CT-M组、CT-H组、DH组小鼠的自由活动次数、筑巢行为评分升高、探索新物体辨别时间明显增加、新旧物体辨别时间比值升高、逃避潜伏期明显缩短、跨平台次数和目标象限停留时间增加(P<0.05).与CT-M组比较,CT-H组小鼠的自由活动次数、筑巢行为评分升高、探索新物体辨别时间增加、新旧物体辨别时间比值升高、逃避潜伏期明显缩短、跨平台次数和目标象限停留时间增加(P<0.05).与DH组比较,CT-H组小鼠的自由活动次数、筑巢行为评分升高、探索新物体辨别时间增加、新旧物体辨别时间比值升高、逃避潜伏期明显缩短、跨平台次数和目标象限停留时间增加(P<0.05).与Model组比较,DH组和CT-M、CT-H组小鼠海马组织中SOD及GSH水平升高,Aβ1-42、p-Tau、NF-κB p65、NLRP3、TNF-α、IL-1β及ROS水平下降,小鼠血清NF-κB p65、NLRP3、TNF-α、IL-1β及ROS水平下降(P<0.05).与CT-L组比较,CT-M组、CT-H组、DH组小鼠海马组织中SOD及GSH水平升高,Aβ1-42、p-Tau、NF-κB p65、NLRP3、TNF-α、IL-1β及ROS水平下降,小鼠血清NF-κB p65、NLRP3、TNF-α、IL-1β及ROS水平下降(P<0.05).与CT-M组比较,CT-H组小鼠海马组织中SOD及GSH水平升高、Aβ1-42、p-Tau、NF-κB p65、NLRP3、TNF-α、IL-1β及ROS水平下降,小鼠血清NF-κB p65、NLRP3、TNF-α、IL-1β及ROS水平下降(P<0.05).与DH组比较,CT-H组小鼠海马组织中SOD及GSH水平升高、Aβ1-42、p-Tau、NF-κB p65、NLRP3、TNF-α、IL-1β及ROS水平下降,小鼠血清NF-κB p65、NLRP3、TNF-α、IL-1β及ROS水平下降(P<0.05).结论:梓醇-川芎嗪方可能通过改善氧化/还原失衡状态,抑制脑内炎症反应从而改善SAMP8小鼠的认知功能障碍,且其量效关系呈正相关.
Objective:To explore the effect of catalpol-tetramethylpyrazine(CT) prescription on cognitive function in SAMP8 mice.Methods:Fifty 14-week-old SAMP8 mice were randomly divided into Model group,low dose CT prescription(CT-L) group,medium dose CT prescription(CT-M) group,high dose CT prescription(CT-H) group and donepezil hydrochloride(DH) group.Ten 14-week-old SAMR1 mice were chosen as Control group.The Control group and Model group were both gavaged with physiological saline,and each medication group was gavaged with corresponding drugs once a day for 8 consecutive weeks.Autonomous activity experiment,nesting behavior experiment,new object recognition experiment,and morris water maze experiment were adopted.After behavioral observations,superoxide dismutase(SOD),glutathione(GSH),β-amyloid protein(Aβ) 1-42,p-Tau,nuclear factor-κB(NF-κB) p65,nucleotide-bound oligomerized domain-like receptor protein 3(NLRP3),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and reactive oxygen species(ROS) levels were detected in the hippocampus of each group.The contents of NF-κB p65,NLRP3,TNF-α,IL-1β,and ROS in serum of each group were detected.Results:Compared with Model group,the number of autonomous activities,nesting behavior scores,the time to distinguish new objects increased,the ratio of time to distinguish new,and old objects increased,the escape latency significantly shortened,the cross-platform number and residence time in the target quarter increased in DH group,CT-M group and CT-H group(P<0.05).Compared with CT-L group,the number of free activities,nesting behavior score increased,the identification time of exploring new objects significantly increased,the ratio of old and new object identification time increased,the escape latency shortened,the cross-platform number and the residence time in the target quarter increased in CT-M group,CT-H group,DH group(P<0.05).Compared with the CT-M group,the number of free activities,the score of nesting behavior,the identification time of exploring new objects,the ratio of old and new objects identification time,the escape latency period,the cross-platform number,and the target quadrant residence time of mice in the CT-H group increased(P<0.05).Compared with DH group,the number of free activities increased,nesting behavior score,identification time of exploring new objects increased,ratio of old and new object identification time increased,escape latency decreased significantly,cross-platform frequency,and target quadrant residence time increased in CT-H group(P<0.05).Compared with Model group,SOD and GSH levels in hippocampus of mice in DH group,CT-M group and CT-H group increased,while Aβ1-42,p-Tau,NF-κB p65,NLRP3,TNF-α,IL-1β,and ROS levels decreased,the levels of serum NF-κB p65,NLRP3,TNF-α,IL-1β,and ROS in mice decreased(P<0.05).Compared with CT-L group,the levels of SOD and GSH in hippocampus of mice in CT-M group,CT-H group and DH group increased,while the levels of Aβ1-42,p-Tau,NF-κB p65,NLRP3,TNF-α,IL-1β and ROS decreased,the levels of serum NF-κB p65,NLRP3,TNF-α,IL-1β,and ROS in mice decreased(P<0.05).Compared with the CT-M group,the levels of SOD and GSH in the hippocampus of mice in the CT-H group increased,and the levels of Aβ1-42,p-Tau,NF-κB p65,NLRP3,TNF-α,IL-1β,and ROS decreased,the levels of serum NF-κB p65,NLRP3,TNF-α,IL-1β,and ROS in mice decreased(P<0.05).Compared with DH group,the levels of SOD and GSH in hippocampus of mice in CT-H group increased,and the levels of Aβ1-42,p-Tau,NF-κB p65,NLRP3,TNF-α,IL-1β,and ROS decreased,the levels of serum NF-κB p65,NLRP3,TNF-α,IL-1β,and ROS in mice decreased(P<0.05).Conclusion:CT prescription could improve the imbalance between oxidation and reduction,inhibit inflammation in the brain,and thus improve cognitive impairment of SAMP8 mice,and the dose-effect relationship is positive.

Alzheimer's diseaseoxidative stresscatalpol-tetramethylpyrazine prescriptionneuroinflammationexperimental study

邓楚珺、孟胜喜、杨若瑜、陈慧泽、杨然、余嘉珞、张博超

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上海交通大学医学院附属第六人民医院 上海 200233

上海交通大学医学院 上海 200025

阿尔茨海默病 氧化应激 梓醇-川芎嗪方 神经炎症 实验研究

2024

中西医结合心脑血管病杂志
中国中西医结合学会 山西医科大学第一医院

中西医结合心脑血管病杂志

CSTPCD
影响因子:1.463
ISSN:1672-1349
年,卷(期):2024.22(21)