摘要
鞘糖脂分子葡萄糖神经酰胺(GluCer)与半乳糖神经酰胺(GalCer),葡萄糖鞘氨醇(GluSph)和半乳糖鞘氨醇(GalSph)分别为异构体。它们均具有细胞毒性,在中枢神经系统(CNS)中积累会导致溶酶体贮积疾病如戈谢病和克拉伯病,也被证实与帕金森氏病和路易体病密切相关。研究CNS中鞘糖脂对神经科学领域具有重要意义。在本文中,我们改进了基于亲和色谱柱的一种液相色谱方法,设计了一个新颖的梯度,可在10min内同时分离检测GluCer/GalCer及GluSph/GalSp异构体。而且,该梯度在每次运行后重新活化分离柱,可将灵敏度(相对等度洗脱)提高一个数量级。本方法成功用于分析疾病小鼠模型的生物样品(包括细胞、脑脊髓液、血浆和脑)中的糖鞘脂,结果表明鞘糖脂可作为研究相关神经退行性疾病的高灵敏生物标志物。
These neutral glycosphingolipids GluCer/GluCer,GluSph/GalSph are stereochemical isomers.They are cytotoxic and their accumulation in the central nervous system(CNS)causes lyso-somal storage disorders like neuronopathic Gaucher's disease(GD)and Krabbe disease(KD).Additionally,loss-of-function mutations in the GBA gene that encodes GCase have been linked to Parkin-son's disease(PD)and Lewy body disorders.To study the CNS glycosphingolipids is critical for neuroscience field.In this paper,we have improved published methods that used a normal phase column called HALO and made it possible to resolve GlcCer/GalCer and GlcSph/GalSph simultaneously in one run within 10 minutes.Importantly,we invented a novel gradient that reactivated the HALO column after each run therefore enhanced the sensitivity by an order of magnitude,which enabled us to analyze the cerebrospinal fluid(CSF)glycosphingolipids in murine models.We have successfully applied this method to multiple disease mouse models and analyzed the brain,CSF,cell and plasma samples.The study demonstrated the potential of this method for biomarker study in multiple neurodegeneration diseases.
作者
邓樱花
曾国平
张洪权
DENG Yinghua;ZENG Guoping;ZHANG Hongquan(Department of Chemistry and Life Science,Hubei University of Education,Wuhan 430205;Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients,Wuhan 430205)
出处
《分析科学学报》
CAS
CSCD
北大核心
2020年第5期759-764,共6页
Journal of Analytical Science
基金
湖北省高等学校优秀中青年科技创新团队计划(No.T201718)。
