Page 74 - 《中国药房》2022年7期

参枣健脑口服液对阿尔茨海默病模型小鼠的神经保护作用及

机制 Δ

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金 衔 ，陈吉聪 ，辛玉英 ，肖洪贺 ，李 妍 ，邓 艳 ，杨静娴 （1.大连市中心医院康复科，辽宁 大连
116000；2.辽宁中医药大学药学院，辽宁 大连 116600）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）07-0836-07
DOI 10.6039/j.issn.1001-0408.2022.07.12
摘 要 目的 研究参枣健脑口服液（SZJN）对阿尔茨海默病（AD）模型小鼠的神经保护作用及机制。方法 将小鼠随机分为假手
术组、模型组、盐酸多奈哌齐片组（0.65 mg/kg）和SZJN低、中、高剂量组（0.3、1.5、7.5 g/kg，以生药量计），每组12只，雌雄各半。各
组小鼠灌胃相应药物（假手术组和模型组小鼠灌胃等体积水），每日2次，连续28 d。在给药第15天时，采用侧脑室注射β-淀粉样
蛋白1-42（Aβ1-42 ）联合腹腔注射氢溴酸东莨菪碱复制AD小鼠模型。采用Morris水迷宫实验检测小鼠的学习记忆能力；采用HE染
色和Nissl染色检测小鼠脑组织病理学变化；检测小鼠脑组织中丙二醛（MDA）和超氧化物歧化酶（SOD）的水平；采用Western blot
法检测小鼠海马组织中环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化水平和脑源性神经营养因子（BDNF）的蛋白表达水平。
结果 与假手术组比较，模型组小鼠逃避潜伏期显著延长，穿越平台次数和目标象限停留时间百分比显著减少（P＜0.01）；脑组织中
SOD水平以及海马组织中CREB蛋白磷酸化水平和BDNF蛋白表达水平均显著降低（P＜0.01），MDA水平显著升高（P＜0.01）；海
马CA1区和皮层组织中神经细胞数量明显减少、排列杂乱且间隙大，细胞核形状不规则且深染，尼氏体模糊不清、排列疏松、数量
减少。与模型组比较，SZJN各剂量组小鼠逃避潜伏期显著缩短，穿越平台次数和目标象限停留时间百分比显著增加（P＜0.01）；
SZJN高剂量组小鼠脑组织中上述指标水平均显著逆转（P＜0.01），脑组织病理损伤均得到改善。结论 SZJN可显著改善AD模型
小鼠的学习记忆能力，减轻脑组织病理损伤和氧化应激，其作用机制可能与激活CREB/BDNF信号通路有关。
关键词 阿尔茨海默病；参枣健脑口服液；神经保护；氧化应激；CREB/BDNF信号通路

Neuroprotective effect and the mechanism of Shenzao jiannao oral liquid on Alzheimer’s disease model
mice
JIN Xian ，CHEN Jicong ，XIN Yuying ，XIAO Honghe ，LI Yan ，DENG Yan ，YANG Jingxian（1. Dept. of
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Rehabilitation，Dalian Central Hospital，Liaoning Dalian 116000，China；2. School of Pharmacy，Liaoning
University of Traditional Chinese Medicine，Liaoning Dalian 116600，China）
ABSTRACT OBJECTIVE To study the neuroprotective effects of Shenzao jiannao oral liquid（SZJN）on Alzheimer’s disease
（AD）model mice and its mechanism. METHODS The mice were randomly divided into sham operation group，model group，
Donepezil hydrochloride tablet group（0.65 mg/kg），SZJN low-dose，medium-dose and high-dose groups（0.3，1.5 and 7.5 g/kg，
calculated by crude drug quantity），with 12 mice in each group，half male and half female. Each group was given relevant
medicine（intragastric administration of water at constant volume in sham operation group and model group），twice a day，for
consecutive 28 d. On the 15th day of administration，intracerebroventricular injection of β-amyloid 1-42（Aβ 1-42 ）combined with
intraperitoneal injection of scopolamine hydrobromide were used to induce AD model. Morris water maze was used to detect the
learning and memory ability of mice. HE staining and Nissl staining were used to evaluate the pathological changes of brain tissue
in mice. The levels of MDA and SOD in brain tissue of mice were detected. The phosphorylation level of cyclic adenosine
monophosphate response element binding protein （CREB） and expression of brain-derived neurotrophic factor （BDNF） in
hippocampal tissues were detected by Western blot. RESULTS Compared with sham operation group，the escape latency of the
model group was significantly prolonged，and the number of crossing the platform and the percentage of residence time in the
target quadrant were significantly reduced（P＜0.01）. The level of SOD in brain tissue，the phosphorylation level of CREB and the
expression level of BDNF in hippocampus decreased significantly（P＜0.01），while the level of MDA increased significantly（P＜
0.01）. In hippocampal CA1 area and cortical tissue，nerve cells showed significantly decreased number，the disordered arrangement
and large gap；the shape of nucleus was irregular and deeply stained，and Nissl body was blurred，loosely arranged and the number
decreased. Compared with model group，the escape latency of mice in each dose group of SZJN was significantly shortened，and
the times of crossing the platform and the percentage of
Δ 基金项目：大连市科技创新基金项目（No.2018J13SN126）
＊主管护师。研究方向：神经康复。E-mail：1127624034@qq.com residence time in the target quadrant were significantly
# 通信作者：教授，博士。研究方向：神经药理学。E-mail：jing- increased （P＜0.01）. Above indexes of brain tissue in mice
xianyang63@126.com were reversed significantly in SZJN high-dose group （P＜

·836 · China Pharmacy 2022 Vol. 33 No. 7 中国药房 2022年第33卷第7期