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第45卷第10期 南京医科大学学报(自然科学版)
2025年10月 Journal of Nanjing Medical University(Natural Sciences) ·1395 ·
·专题研究:神经退行性疾病·
基于秀丽线虫转基因株系探究牛蒡多糖对阿尔茨海默病的作
用及机制
裴雨晴 ,邵歆迪 ,朱煜洁 ,成 飞 ,周珈珲 ,朱欣童 ,麻瑞莹 ,陈菲菲 ,施 萱 ,李露娜 ,李鑫颖 ,
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徐纯钰 ,张亦唐 ,周思玥 ,申 丽 ,李华玲 1,3*
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扬州大学医学部,兽医学院,中西医结合老年病防治省高校重点实验室,江苏 扬州 225001
[摘 要] 目的:基于阿尔茨海默病(Alzheimer’s disease,AD)秀丽线虫病理模型,探讨牛蒡多糖在AD中的作用。方法:采用
课题组自制的牛蒡多糖,不同浓度(62.5、125.0、250.0 μg/mL)作用于AD线虫病理株系(CL4176、CL2355、CL2006),研究其对线
虫β淀粉样蛋白(amyloid beta,Aβ)沉积、趋化行为、5⁃羟色胺敏感性、瘫痪、生长发育、运动能力、摄食能力各项行为学指标的影
响,测定氧化应激与胆碱能神经元相关指标,荧光定量PCR检测线虫体内相关基因的表达水平。结果:牛蒡多糖具多重生物
活性,可以减少Aβ蛋白的水平与沉积,降低5⁃羟色胺敏感性,强化线虫趋化行为和学习记忆能力,延迟瘫痪发生时间,促进发
育,增加摆动与咽部震动频率,提高抗氧化酶活性,降低乙酰胆碱酯酶(acetylcholinesterase,AChE)活性。同时,其可降低age⁃1
和akt⁃1基因的表达,增强daf⁃16基因的表达,促进skn⁃1、gst⁃4、sod⁃1和sod⁃2表达,发挥抗氧化作用,减轻AD症状。此外,牛蒡
多糖还抑制ace⁃1和ace⁃2基因表达,降低AChE活性。结论:牛蒡多糖可能通过调节age⁃1/akt⁃1/daf⁃16信号通路,降低氧化应
激水平,同时抑制AChE活性,从而缓解并改善AD相关病理过程。
[关键词] 阿尔茨海默病;秀丽线虫转基因株系;牛蒡多糖;抗氧化性;乙酰胆碱酯酶抑制剂
[中图分类号] R749.1 [文献标志码] A [文章编号] 1007⁃4368(2025)10⁃1395⁃09
doi:10.7655/NYDXBNSN250508
ThemechanismsofburdockpolysaccharideonAlzheimer’sdiseasebasedon Caenorhabditis
elegans
PEI Yuqing ,SHAO Xindi ,ZHU Yujie ,CHENG Fei ,ZHOU Jiahui ,ZHU Xintong ,MA Ruiying ,CHEN Feifei ,
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SHI Xuan ,LI Luna ,LI Xinying ,XU Chunyu ,ZHANG Yitang ,ZHOU Siyue ,SHEN Li ,LI Hualing 1,3*
1 Faculty of Medicine,College of Veterinary Medicine,Key Laboratory of the Jiangsu Higher Education Institutions
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for Integrated Traditional Chinese and Western Medicine in Senile Diseases Control,Yangzhou University,Yangzhou
225001,China
[Abstract] Objective:This study aimed to investigate the therapeutic effect of burdock polysaccharide on Alzheimer’s disease(AD)
using Caenorhabditis elegans(C. elegans)pathology model. Methods:Burdock polysaccharide made in our lab was used at varying
concentrations(62.5,125.0,and 250.0 μg/mL)on transgenic C. elegans AD models(CL4176,CL2355,and CL2006 strains)to study
the effects on nematode amyloid beta(Aβ)deposition,chemotaxis,5⁃hydroxytryptamine sensitivity,paralysis,growth and development,
locomotor activity,feeding ability. Oxidative stress and cholinergic neuron⁃related indexes were measured,and the expression levels
of related genes in nematodes were examined by RT⁃PCR. Results:Burdock polysaccharide exhibited multiple biological activities,
thus reducing the level and deposition of Aβ protein,reducing 5⁃hydroxytryptamine sensitivity,strengthening nematode chemotaxis and
learning memory,delaying paralysis,promoting development,increasing swing and pharyngeal vibration frequency,increasing
antioxidant enzyme activity and reducing acetylcholinesterase(AChE)activity. Meanwhile,it reduced the expression of age⁃1 and akt⁃1
genes,enhanced the expression of daf⁃16 gene,promoted the expression of skn⁃1,gst⁃4,sod⁃1 and sod⁃2,exert antioxidant effects,and
[基金项目] 国家自然科学基金(81671056);江苏省中医药科技发展计划项目(MS2023177);扬州大学大学生科技创新基金
(XCX20250859)
通信作者(Corresponding author),E⁃mail:hlli@yzu.edu.cn(ORCID:0000⁃0002⁃9416⁃7770)
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