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
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1扬州大学医学部,2兽医学院,3中西医结合老年病防治省高校重点实验室,江苏 扬州 225001

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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)


The mechanisms of burdock polysaccharide on Alzheimer’s disease based on Caenorhabditis elegans
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1Faculty of Medicine,2College of Veterinary Medicine,3Key Laboratory of the Jiangsu Higher Education Institutionsfor Integrated Traditional Chinese and Western Medicine in Senile Diseases Control,Yangzhou University,Yangzhou 225001 ,China

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    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-1akt-1基因的表达,增强daf-16基因的表达,促进skn-1、gst-4、sod-1sod-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-1ace-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。

    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 alleviated AD symptoms. Concurrently,it attenuated AD pathology by inhibiting ace -1/ace -2 expression,and reducing AChE activity. Conclusion:Burdock polysaccharide may alleviate and improve AD-related pathological processes by regulating the age-1/akt-1/daf-16 signaling pathway to reduce oxidative stress levels while inhibiting AChE activity.

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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,徐纯钰,张亦唐,周思玥,申丽,李华玲.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[J].南京医科大学学报(自然科学版),2025,(10):1395-1403

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  • 收稿日期:2025-04-29
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  • 在线发布日期: 2025-10-16
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