期刊文献+

石胆草碳苷B改善阿尔茨海默病小鼠模型的研究

Carbon glycosides of Corallodiscus flabellata B.L.Burtt ameliorate the Alzheimer’s disease in mice
原文传递
导出
摘要 目的:探究石胆草碳苷B(CB)对淀粉样β蛋白片段25-35(Aβ_(25-35))诱导阿尔茨海默病(AD)的干预作用及其作用机制,为临床治疗AD提供实验基础。方法:将40只雄性昆明小鼠随机分为正常组、模型组、多奈哌齐组(10 mg·kg^(-1))、CB组(10 mg·kg^(-1))。除正常组外,其余各组小鼠脑内注射Aβ_(25-35)(300μmol·L^(-1))建立AD小鼠模型。Y迷宫、新物体识别实验检测小鼠学习记忆能力;HE染色、尼氏染色和电镜观察海马病理变化;酶联免疫吸附法检测脑内Aβ_(1-42)/Aβ_(1-40)、磷酸化Tau蛋白(p-Tau)水平;生化法检测血清中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的含量或活性;流式细胞术检测脑内活性氧(ROS)水平;蛋白免疫印迹法(WB)检测脑内LC_(3)B,Beclin-1和P62相关自噬蛋白水平。体外培养PC-12细胞,结合自噬抑制剂3-甲基腺嘌呤(3-MA),观察CB对Aβ_(25-35)诱导PC-12细胞的影响是否与自噬有关,从而进一步阐释CB干预AD的作用机制。结果:行为学结果显示CB可显著改善Aβ_(25-35)诱导小鼠的学习记忆能力,HE及尼氏染色显示CB可显著改善海马损伤及神经元萎缩,试剂盒检测结果显示CB可显著降低小鼠脑内Aβ_(1-42)/Aβ_(1-40),p-Tau和氧化应激水平,WB结果显示CB可显著增强自噬水平;体外实验结果表明,CB可显著提高PC-12细胞迁移能力及增殖能力,但在加入3-MA后其作用显著减弱。结论:CB可能通过增强自噬来减轻Aβ_(25-35)诱导的AD模型损伤。 Objective:To explore the intervention effect and its mechanism of carbon glycosides from Corallodiscus flabellata B.L.Burtt(CB)on Alzheimer’s disease(AD)induced by amyloid-β_(25-35)(Aβ_(25-35))in mice,and provide experimental basis for clinical treatment of AD.Methods:Forty male Kunming mice were randomly divided into control group,model group,Donepezil group(10 mg·kg^(-1))and CB group(10 mg·kg^(-1)).Except for the control group,the mice in other groups were injected intracerebroventricularly(ICV)by Aβ_(25-35)(300μmol·L^(-1))peptides to form Alzheimer’s disease model.The ability of learning and memory,as well as anxiety state of mice were measured by Y maze and new object recognition experiments.The pathological changes of hippocampus were detected by HE staining,Nissl staining and electron microscope.The serum levels of Aβ_(1-42)/Aβ_(1-40) and p-Tau were detected by enzyme-linked immunosorbent assay.The contents of MDA,SOD,GSH-Px in serum were detected by biochemical method.The level of ROS was detected by Flow sight.The expressions of LC3 B,Beclin-1 and P62 in brain were detected by Western blot.Whether the effect of CB on PC-12 cells induced by amyloid-β_(25-35)(Aβ_(25-35))is related to autophagy is studied in in cultured PC-12 cells in vitro,combined with autophagy inhibitor 3-methyladenine(3-MA),so as to further explain the mechanism of CB intervention in AD.Results:Behavioral results showed that CB significantly improved the learning memory ability of Aβ_(25-35)-induced mice.HE and Nissl results showed that CB significantly improved hippocampal damage and neuronal atrophy.The kit assay results showed that CB significantly reduced the levels of Aβ_(1-42)/Aβ_(1-40) and p-Tau and oxidative stress in mouse brain.The WB results showed that CB significantly enhanced autophagy level.In vitro experiments showed that CB significantly improved the migration and proliferation of PC-12 cells;however,the effect was significantly weakened after the addition of 3-MA.Conclusion:CB reduced the symptoms of Alzheimer’s disease in mice induced by amyloid-β25-35(Aβ_(25-35))possibly via enhancing autophagy.
作者 张宇涵 李孟 曾梦楠 郭彭莉 刘萌 梁家宝 曹兵 郑晓珂 冯卫生 ZHANG Yu-han;LI Meng;ZENG Meng-nan;GUO Peng-li;LIU Meng;LIANG Jia-bao;CAO Bing;ZHENG Xiao-ke;FENG Wei-sheng(Henan University of Chinese Medicine,Zhengzhou 450046,China;The Engineering and Technology Center for Chinese Medicine Development of HenanProvince,Zhengzhou 450046,China)
出处 《中国新药杂志》 CAS CSCD 北大核心 2022年第17期1718-1726,共9页 Chinese Journal of New Drugs
基金 国家重点研发计划-中医药现代化研究专项(2019YFC1708802) 河南省高层次人才特殊支持计划“中原千人计划”-中原领军人才(ZYQR201810080)。
关键词 阿尔茨海默病 淀粉样β蛋白片段25-35 黄酮碳苷 自噬 3-甲基腺嘌呤 Alzheimer’s disease amyloid-β25-35 flavone C-glycosides autophagy 3-methyladenine
  • 相关文献

参考文献13

二级参考文献126

共引文献118

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部