人参皂苷Re对阿尔茨海默病模型小鼠脑组织生物标记物调控作用的研究  

Protective effect of ginsenoside Re on biomarkers in mice with Alzheimer's disease

作　　者：李菁媛[1] 王喆[1] 刘颖[2] 李伟 李乃静[1] LI Jing-yuan WANG Zhe LIU Ying LI Wei LI Nai-jing(Department of Gerontology, Shengjing Hospital of China Medical University, Shenyang 110004, China Department of Emergency Medicine, Laboratory of PLA Wound and Trauma Center, the General Hospital of Shenyang Military, Shenyang 110016, China College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China)

机构地区：[1]中国医科大学附属盛京医院干诊科,辽宁省沈阳市110004 [2]沈阳军区总医院急诊医学部全军重症战创伤救治中心实验室,辽宁省沈阳市110016 [3]沈阳药科大学药学院药物分析教研室,辽宁省沈阳市110016

出　　处：《实用老年医学》2017年第10期921-926,共6页Practical Geriatrics

基　　金：国家自然科学基金(81203002)

摘　　要：目的通过超高速液相色谱-质谱联用(UPLC-MS)技术研究人参皂苷Re(G-Re)对阿尔茨海默病(AD)模型小鼠生物标记物的调控作用以及机制,为AD的中药治疗提供新思路。方法将小鼠随机分为对照组、AD模型组和G-Re治疗组,通过免疫组化实验观察小鼠脑部海马区细胞的病理学改变,运用以UPLC-MS为基础的代谢组学技术研究G-Re对AD模型小鼠脑组织生物标记物的调控作用。结果免疫组化实验发现,对照组小鼠海马区无Aβ沉积,AD模型组小鼠海马区可见大量Aβ沉积,经G-Re治疗后小鼠海马区Aβ沉积明显减少。代谢组学分析发现,AD模型组小鼠脑组织中存在次黄嘌呤、次黄嘌呤核苷、苯丙氨酸、16碳鞘氨醇、植物鞘氨醇、溶血磷脂酰胆碱C16:0、溶血磷脂酰胆碱C18:1、溶血磷脂酰胆碱C18:0等9种生物标记物。与对照组比较,AD组次黄嘌呤、次黄嘌呤核苷和苯丙氨酸的含量明显升高(P<0.05),16碳鞘氨醇、植物鞘氨醇、溶血磷脂酰胆碱(C16:0、C18:1、C18:0)的含量明显降低(P<0.05)。经G-Re干预后,AD组小鼠脑组织中次黄嘌呤、次黄嘌呤核苷和苯丙氨酸的含量明显降低(P<0.05),16碳鞘氨醇、植物鞘氨醇、溶血磷脂酰胆碱(C16:0、C18:1、C18:0)的含量明显升高(P<0.05)。结论 G-Re可以干预AD小鼠体内氨基酸、核酸及脂质等代谢途径,减少小鼠海马区的Aβ沉积,从而对AD起到治疗作用。Objective To investigate the effect of ginsenoside Re（ G-Re） on biomarkers in an Alzheimer＇s disease（ AD） mouse model based on UPLC-MS,and to provide new ideas for traditional Chinese medicine treatment of AD. Methods Twenty-four mice were randomly divided into control group,AD model group and G-Re treatment group with eight mice in each group. Pathological changes in the hippocampus were assessed by immunohistochemistry. UPLC/MS-based metabolomics was used to identify biomarkers which were differentially expressed in the brains of AD mice. Results The hippocampal amyloid deposition increased in AD mice,and it was ameliorated by the treatment of G-Re.A total of 9 potential biomarkers were identified,which were associated with the metabolism of purine,amino acids,sphingolipids and lysophosphatidylcholines in AD mice. Compared to control group,the peak intensities of 9 biomarkers give a pronounced change in AD（ P〈0. 05）. G-Re treatment affected all these metabolic pathways. Conclusions These results indicate that G-Re can reduce the hippocampal amyloid deposition in AD mice by regulation of related brain metabolic pathways. In a word,G-Re plays a positive role in the treatment of AD.

关 键 词：人参皂苷RE 阿尔茨海默病 生物标记物 超高速液相色谱-质谱联用 

分 类 号：R749.16[医药卫生—神经病学与精神病学]