Page 52 - 《中国药房》2022年10期

黄水枝醇提物对小鼠学习记忆障碍的影响及作用机制 Δ

蒋先慧 ，张金娟 ，周 涛 ，廖尚高 ，何 迅 （1.贵州医科大学药学院，贵阳 550025；2.贵州医科大学基础医
1
1 #
2
1
1＊
学院，贵阳 550025）
中图分类号 R965；R285 文献标志码 A 文章编号 1001-0408（2022）10-1198-06
DOI 10.6039/j.issn.1001-0408.2022.10.08

摘 要 目的 探究黄水枝醇提物（以下简称“TPE”）对小鼠学习记忆障碍的影响及作用机制。方法 将雄性昆明小鼠随机分为正
常组、模型组、阳性组（盐酸多奈哌齐4 mg/kg）和TPE低、中、高剂量组（150、300、600 mg/kg），每组10只。给药组小鼠每天灌胃相
应药液1次，正常组和模型组小鼠每天灌胃水1次，连续22 d；第17天，给药组与模型组小鼠腹腔注射氢溴酸东莨菪碱（3 mg/kg）以
建立学习记忆障碍模型。以Morris水迷宫实验对小鼠空间学习记忆能力进行评估，以苏木精-伊红染色对小鼠海马组织细胞形态
进行观察，检测各组小鼠脑组织中乙酰胆碱酯酶（AChE）、乙酰胆碱转移酶（ChAT）、超氧化物歧化酶（SOD）、丙二醛（MDA）、白细
胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）水平以及海马组织中磷酸化Tau蛋白（p-Tau）、β淀粉样前体蛋白裂解酶1（BACE1）、淀粉
样前体蛋白（APP）的相对表达量。结果 阳性组和TPE中、高剂量组小鼠的逃避潜伏期（训练第4～5天）均较模型组显著缩短，穿
过平台次数和目标象限运动距离百分比均较模型组显著升高（P＜0.05）。与模型组比较，各给药组小鼠海马CA1区中神经元有所
增多，固化萎缩状态的神经元有所减少，神经元排列趋于紧密；阳性组和TPE中、高剂量组小鼠脑组织中ChAT、SOD水平均显著
升高，AChE、MDA、IL-6、TNF-α水平和海马组织中p-Tau、BACE1、APP蛋白的相对表达量均显著降低（P＜0.05）。结论 TPE可改
善东莨菪碱诱导的小鼠学习记忆障碍，其机制可能与平衡大脑胆碱能系统，缓解氧化应激损伤，改善炎症反应，抑制 p-Tau、
BACE1、APP蛋白的过度表达有关。
关键词 黄水枝醇提物；学习记忆障碍；乙酰胆碱酯酶；东莨菪碱；小鼠

Effects and mechanism of the ethanol extract of Tiarella polyphylla on learning and memory impairment in
mice
1
2
1
JIANG Xianhui ，ZHANG Jinjuan ，ZHOU Tao ，LIAO Shanggao ，HE Xun（1. College of Pharmacy，Guizhou
1
1
Medical University， Guiyang 550025， China； 2. School of Basic Medical Sciences， Guizhou Medical
University，Guiyang 550025，China）
ABSTRACT OBJECTIVE To investigate the effects and mechanism of the ethanol extract of Tiarella polyphylla（“TPE”）on
learning and memory impairment in mice. METHODS Male Kunming mice were randomly divided into normal group，model
group，positive group（donepezil hydrochloride 4 mg/kg）and TPE low-dose，medium-dose and high-dose groups（150，300，600
mg/kg），with 10 mice in each group. Drug administration groups were given relevant medicine intragastrically once a day，and
normal group and model group were given water intragastrically once a day，for consecutive 22 d. On the 17th day，administration
groups and model group were intraperitoneally injected with scopolamine hydrobromide（3 mg/kg）to establish a model of learning
and memory impairment. The learning and memory ability of the mice were evaluated by the Morris water maze. Hematoxylin-eosin
（HE） staining was used for morphological observation of hippocampus cells of the mice. The levels of acetylcholinesterase
（AChE），choline acetyltransferase（ChAT），superoxide dismutase（SOD），malondialdehyde（MDA），interleukin-6（IL-6）and
tumor necrosis factor-α（TNF-α）in cerebral tissue as well as the relative expression of phosphorylated Tau protein（p-Tau），β-site
amyloid precursor protein cleaving enzyme 1（BACE1） and amyloid precursor protein （APP） in hippocampus tissue were all
detected. RESULTS The escape latency of mice in positive group，TPE medium-dose and high-dose groups were all significantly
shortened than the model group on the 4th to 5th day of training，while the times of crossing platform and the percentage of
movement distance in target quadrant were significantly increased （P＜0.05）. Compared with model group，the neurons in the
hippocampal CA1 region of mice were increased to varying degrees in administration groups，the neurons in solidified and atrophic
state decreased，and the arrangement of neurons tended to be
Δ 基金项目：贵州省科技计划项目科技创新人才团队（No.黔科合
close；the levels of ChAT and SOD in cerebral tissue were
平台人才〔2020〕5006）
significantly increased in positive group and TPE medium-dose
＊硕士研究生。研究方向：中药制剂工艺及质量控制。E-mail：
jxh53594@163.com and high-dose groups；the levels of AChE，MDA，IL-6，the
# 通信作者：教授，硕士生导师，硕士。研究方向：中药物质基础 levels of TNF-α and relative expression of p-Tau，BACE1 and
及质量控制。E-mail：2812878586@qq.com APP in hippocampus tissue were decreased significantly（P＜

·1198 · China Pharmacy 2022 Vol. 33 No. 10 中国药房 2022年第33卷第10期