异槲皮苷对β-淀粉样蛋白诱导毒性的阿尔茨海默病转基因秀丽隐杆线虫模型的神经保护作用  

Neuroprotective Effect of Isoquercitrin onβ-Amyloid-induced Toxicity in a Transgenic Caenorhabditis elegans Model of Alzheimer′s Disease

作　　者：李冰琪 侯晓梦 杨扬 刘傲雪 李强[1] LI Bing-qi;HOU Xiao-meng;YANG Yang;LIU Ao-xue;LI Qiang(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学中药学院,北京100029

出　　处：《中国现代中药》2023年第9期1934-1939,共6页Modern Chinese Medicine

基　　金：国家重点研发计划项目(2018YFC1706500)。

摘　　要：目的:探究探讨异槲皮苷对β-淀粉样蛋白(Aβ)诱导毒性的转基因CL4176秀丽隐杆线虫(以下简称线虫)的神经保护作用及其作用机制。方法:以转基因线虫CL4176为模型,在显微镜下考察异槲皮苷对线虫瘫痪情况、寿命、运动能力、吞咽频率、活性氧(ROS)水平、抗氧化酶活力等指标的影响。采用实时荧光定量技术测定异槲皮苷作用后线虫Aβ沉积及胰岛素信号途径相关基因表达情况。结果:异槲皮苷能够显著降低痴呆模型线虫瘫痪率(P<0.05),可延长模型线虫寿命,提高其运动能力,能够显著提高模型线虫体内超氧化物歧化酶和过氧化氢酶的活力(P<0.05),显著降低其体内ROS和丙二醛水平(P<0.05),同时显著下调Aβ mRNA表达量,上调DAF-16、SKN-1、SOD-3、GST-4、CTL-3、HSF-1 mRNA表达量。结论:异槲皮苷能够显著延缓线虫衰老、降低瘫痪率和抑制Aβ沉积,可能与调控胰岛素/胰岛素样生长因子1信号通路上的基因表达有关。Objective:To explore the neuroprotective effect of isoquercitrin onβ-amyloid(Aβ)-induced toxicity in the transgenic Caenorhabditis elegans CL4176 model of Alzheimer's disease and decipher the underlying mechanism.Methods:The effects of isoquercitrin on the paralysis,lifespan,exercise ability,swallowing frequency,reactive oxygen species(ROS)level,antioxidant enzyme activity and other indicators of the transgenic nematode model were investigated under a microscope.The real-time fluorescent quantitative RCR was employed to measure the expression of the genes involved in Aβdeposition and insulin signaling pathway in nematodes.Results:Isoquercitrin reduced the paralysis rate(P<0.05),prolonged the lifespan,improved the exercise ability,increased the activities of superoxide dismutase and catalase(P<0.05),and lowered the ROS and malondialdehyde levels(P<0.05)in the model nematode.Furthermore,it significantly downregulated the mRNA level of Aβand up-regulated the mRNA levels of DAF-16,SKN-1,SOD-3,GST-4,CTL-3,AND HSF-1.Conclusion:Isoquercitrin can significantly delay aging,reduce the paralysis rate,and inhibit Aβdeposition by regulating the expression of genes in the insulin/insulin-like growth factor-1(IGF-1)signaling pathway.

关 键 词：异槲皮苷 神经保护 作用机制 秀丽隐杆线虫 阿尔茨海默病 

分 类 号：R285.5[医药卫生—中药学]