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沙利度胺对阿尔茨海默病秀丽隐杆线虫模型的改善作用及机制 Δ

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方亚影 ，阎茹玉 ，李玉贤 ，吴宿慧 ，李寒冰 ，李根林（1.河南中医药大学药学院，郑州 450046；2.河南中医
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药大学河南省仲景方药健康衰老产业工程研究中心，郑州 450046）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）11-1324-06
DOI 10.6039/j.issn.1001-0408.2022.11.08
摘 要 目的 研究沙利度胺对阿尔茨海默病（AD）线虫模型的改善作用及机制。方法 以BR5270品系秀丽隐杆线虫（以下简称
“线虫”）为AD模型动物，BR5271品系线虫为对照。利用基础慢反应实验研究沙利度胺（0.5、2.0、6.0、15.0 mg/mL）对BR5270品系
线虫运动能力的影响；利用寿命实验研究沙利度胺（0.5、2.0、6.0、15.0 mg/mL）对BR5270品系线虫寿命的影响；利用短期、长期学
习记忆实验研究沙利度胺（0.5、2.0、6.0 mg/mL）对BR5270品系线虫学习记忆能力的影响；采用实时荧光定量聚合酶链式反应技术
研究沙利度胺（0.5、2.0、6.0 mg/mL）对 BR5270 品系线虫体内磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）信号通路相关基因
（Age-1、Akt-1、Gsk-3）和钙蛋白酶同源基因（Clp-1）的mRNA表达的影响。结果 经沙利度胺干预后，BR5270品系线虫30 s内的摆
动次数显著增加（0.5 mg/mL 组除外），10％最大寿命显著延长（仅 0.5 mg/mL 组），短期、长期学习指数均显著升高（仅 6.0 mg/mL
组），体内Age-1、Akt-1基因（0.5、2.0 mg/mL组除外）mRNA表达水平均显著升高，Gsk-3（0.5 mg/mL组除外）、Clp-1基因mRNA表
达水平均显著降低（P＜0.05或P＜0.01）。结论 沙利度胺可改善AD线虫模型的运动障碍，并延长其寿命，增强其学习记忆能力；
具体作用机制可能与激活PI3K/Akt信号通路和抑制钙蛋白酶有关。
关键词 沙利度胺；秀丽隐杆线虫；阿尔茨海默病；磷脂酰肌醇3-激酶/蛋白激酶B信号通路

Improvement effects and mechanism of thalidomide on Alzheimer’s disease model of Caenorhabditis
elegans
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FANG Yaying ，YAN Ruyu ，LI Yuxian ，WU Suhui ，LI Hanbing ，LI Genlin（1. College of Pharmacy，Henan
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University of Chinese Medicine，Zhengzhou 450046，China；2. Henan Engineering Research Center of Zhang
Zhongjing’s Formula Medicine Health and Aging Industry，Henan University of Chinese Medicine，Zhengzhou
450046，China）
ABSTRACT OBJECTIVE To study the improvement effects and mechanism of thalidomide on Alzheimer’s disease（AD）model
of Caenorhabditis elegans. METHODS In this study，the BR5270 strain of C. elegans was used as AD model and BR5271 strain as
the control. The effects of thalidomide（0.5，2.0，6.0，15.0 mg/mL）on the motility of BR5270 strains of C. elegans were studied by
the basal slowing response assay；the effects of thalidomide（0.5，2.0，6.0，15.0 mg/mL）on the survival time of BR5270 strain of
C. elegans were studied by life assay；the effects of thalidomide（0.5，2.0，6.0 mg/mL）on learning and memory ability of BR5270
strain of C. elegans were studied by short-term and long-term learning and memory assay. RT-PCR technology was used to study
the effects of thalidomide（0.5，2.0，6.0 mg/mL）on mRNA expression of phosphatidylinositol 3-kinase（PI3K）/protein kinase B
（Akt）signal pathway related genes（Age-1，Akt-1，Gsk-3）and calpain homologous gene（Clp-1）in BR5270 strain of C. elegans.
RESULTS After the intervention of thalidomide，oscillation times of BR5270 strain of C. elegans increased significantly within 30 s
（except for 0.5 mg/mL group），and the 10％ of maximum life span was prolonged significantly（only 0.5 mg/mL group）；the
short-term and long-term learning indexes were improved significantly（only 6.0 mg/mL group）；mRNA expression of Age-1 and
Akt-1（except for 0.5，2.0 mg/mL groups）were increased significantly，mRNA expression of Gsk-3（except for 0.5 mg/mL group）
and Clp-1 were decreased（P＜0.05 or P＜0.01）. CONCLUSIONS Thalidomide can ameliorate the dyskinesia of AD model of C.
elegans，prolong the lifespan of this strain，and enhance its learning and memory ability. Its mechanism of action may be related to
activation of PI3K/Akt signaling pathway and inhibition of calpain.
KEYWORDS thalidomide； Caenorhabditis elegans；
Δ 基金项目：河南省科技发展计划项目（No.212102310347）
Alzheimer’s disease；phosphatidylinositol 3-kinase/protein
＊硕士研究生。研究方向：药物活性。E-mail：710279109@qq.
com kinase B signal pathway
# 通信作者：教授，硕士生导师，博士。研究方向：中药药理学。
电话：0317-65962746。E-mail：iwusuhui@163.com

·1324 · China Pharmacy 2022 Vol. 33 No. 11 中国药房 2022年第33卷第11期