Page 40 - 《中国药房》2022年24期

基于肠脑轴探讨地黄饮子对 APP/PS1 转基因阳性小鼠神经功能

的改善作用及机制
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陈 靖 ，梁喜才 ，王 健 ，王生化 ，宁天一（1.辽宁中医药大学教学实验中心，沈阳 110847；2.辽宁中医药
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大学实验动物中心，沈阳 110847）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）24-2978-07
DOI 10.6039/j.issn.1001-0408.2022.24.07

摘 要 目的 探讨地黄饮子对APP/PS1转基因阳性小鼠神经功能的改善作用及可能机制。方法 将APP/PS1转基因阳性小鼠随
机分为 APP/PS1 阳性模型组，地黄饮子低、中、高剂量（12、24、48 g/kg，按生药量计）组和西药组（盐酸多奈哌齐 0.8 mg/kg），并以
APP/PS1转基因阴性小鼠作为APP/PS1阴性正常组，每组6只。各药物组小鼠灌胃相应药液，APP/PS1阳性模型组和APP/PS1阴
性正常组小鼠灌胃同体积生理盐水，每天1次，连续28 d。末次给药后，考察各组小鼠的学习和记忆能力，肠道菌群多样性（仅地
黄饮子中剂量组）、海马组织神经细胞病理改变，以及Bcl-2、Bax、脑源性神经营养因子（BDNF）的表达情况。结果 与APP/PS1阳
性模型组比较，地黄饮子中、高剂量组小鼠的逃逸潜伏期显著缩短，穿过原平台次数显著增加（P＜0.05）。与其余组比较，地黄饮
子中剂量组的Chao1指数更低，Shannon指数更高（P＜0.05），且其微生物菌群的操作分类单位（OTU）丰度有所降低，优势菌种为
梭菌纲o_Clostridia_vadinBB60_group、疣微菌g_UCG_005。与APP/PS1阳性模型组比较，地黄饮子中、高剂量组小鼠海马CA1区
神经细胞病理改变有所改善，其海马组织中 Bcl-2、BDNF 蛋白的表达均显著上调，Bax 蛋白的表达均显著下调（P＜0.05）。结论
地黄饮子可增强肠道菌群多样性，改变优势菌种，并能抑制大脑神经细胞凋亡，提高BDNF水平；其作用机制可能是借助肠脑轴来
保护神经细胞，从而提高APP/PS1阳性模型小鼠的学习和认知能力。
关键词 地黄饮子；肠脑轴；神经功能；学习记忆能力；APP/PS1转基因阳性小鼠

Investigation of the improvement effect of Dihuang yinzi on neurological function of APP/PS1 double
transgenic positive mice based on gut-brain axis and its mechanism
CHEN Jing ，LIANG Xicai ，WANG Jian ，WANG Shenghua ，NING Tianyi（1. Teaching Experiment Center of
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Liaoning University of Traditional Chinese Medicine，Shenyang 110847，China；2. Experimental Animal Center of
Liaoning University of Traditional Chinese Medicine， Shenyang 110847，China）
ABSTRACT OBJECTIVE To investigate the improvement effect of Dihuang yinzi on neurological function of APP/PS1 double
transgenic positive mice and its possible mechanism. METHODS APP/PS1 double transgenic positive mice were randomly divided
into APP/PS1 positive model group， Dihuang yinzi low-dose， medium-dose and high-dose groups （12， 24， 48 g/kg，by the amount
of crude drug）， western medicine group （donepezil hydrochloride 0.8 mg/kg）； APP/PS1 transgenic negative mice were included in
as APP/PS1 negative normal group， with 6 mice in each group. Administration groups were given relevant medicine
intragastrically； APP/PS1 positive model group and APP/PS1 negative normal group were given constant volume of normal saline
intragastrically， once a day， for consecutive 28 d. After the last medication， the ability of learning and memory， intestinal flora
diversity （only medium-dose group of Dihuang yinzi）， pathological changes of neural cells in hippocampus， and the expressions of
Bcl-2， Bax and brain-derived neurotrophic factor （BDNF） in mice of each group were investigated. RESULTS Compared with
APP/PS1 positive model group， escape latency of mice was shortened significantly in Dihuang yinzi medium-dose and high-dose
groups， while the times of crossing the platform significantly increased （P＜0.05）. Compared with APP/PS1 positive model group，
Chao1 index of Dihuang yinzi medium-dose group was lower， while Shannon index was higher （P＜0.05）； OTU abundance of
microbial flora was decreased to some extent； dominant flora was Clostridia o_ Clostridia_ vadinBB60_ Group， verruca G_ UCG_
005. Compared with the APP/PS1 positive model group， the pathological changes of the nerve cells in the hippocampal CA1 area of
mice were improved in the medium-dose and high-dose groups of Dihuang yinzi； the protein expressions of Bcl-2 and BDNF in the
hippocampal tissue were significantly increased， while the protein expression of Bax was significantly decreased （P＜0.05）.
CONCLUSIONS Dihuang yinzi can enhance the diversity of flora， change the type of dominant flora， and can inhibit the
apoptosis of brain neurons， and increase the level of BDNF； its mechanism may be to protect nerve cells by means of gut-brain
axis， thereby improving the learning and memory ability of APP/PS1 positive model mice.
KEYWORDS Dihuang yinzi； gut-brain axis； neurological
Δ 基金项目 辽宁省自然科学基金计划指导计划项目（No.2019-
function； learning and memory ability； APP/PS1 double
ZD-0434）
transgenic positive mice
＊第一作者 高级实验师，硕士。研究方向：经方药理学。电话：
024-31207016。E-mail：tgsy2018@163.com

· 2978 · China Pharmacy 2022 Vol. 33 No. 24 中国药房 2022年第33卷第24期