垂穗披碱草中黄酮类化合物的分离及其对高脂血症斑马鱼脂质代谢的影响  

Isolation of Flavonoids from Elymus nutans Griseb and Their Effects on Lipid Metabolism in Hyperlipidemic Zebrafish

作　　者：童莹莹 初明 党军[2,3] 黄海辉 马成俊 李刚[1] TONG Yingying;CHU Ming;DANG Jun;HUANG Haihui;MA Chengjun;LI Gang(School of Life Sciences,Center for Mitochondria and Healthy Aging,Yantai University,Yantai 264005,China;Northwest Institute of Plateau Biology,Chinese Academy of Sciences,Xining 810001,China;Qinghai Provincial Key Laboratory of Tibetan Medicine Research,Xining 810001,China)

机构地区：[1]烟台大学生命科学学院,烟台大学线粒体与健康衰老研究中心,山东烟台264005 [2]中国科学院西北高原生物研究所,青海西宁810001 [3]青海省藏药研究重点实验室,青海西宁810001

出　　处：《烟台大学学报(自然科学与工程版)》2025年第1期64-73,共10页Journal of Yantai University(Natural Science and Engineering Edition)

基　　金：山东省自然科学基金资助项目(ZR2020MH380);烟台市科技创新发展计划项目(2021XDHZ078)。

摘　　要：旨在从垂穗披碱草(Elymus nutans Griseb.)中分离黄酮类化合物,并研究其对高脂饮食诱导的高脂血症斑马鱼脂质代谢的影响。采用中高压液相色谱结合二维液相色谱等方法进行分离纯化,利用核磁共振波谱(NMR)、质谱(MS)等技术鉴定化合物结构;建立高脂饮食诱导的斑马鱼幼鱼高脂血症模型,化合物持续喂养5 d后,检测各组斑马鱼幼鱼的存活率、体重、体长、BMI的变化;油红O染色、HE染色分别观察脂质积累情况和组织病理学变化;生化试剂盒测定总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-c)、高密度脂蛋白胆固醇(HDL-c);实时荧光定量PCR(qRT PCR)检测脂质代谢相关mRNA的表达变化。从垂穗披碱草中分离得到2个黄酮类同分异构体化合物,分别鉴定为夏佛塔苷和异夏佛塔苷。夏佛塔苷和异夏佛塔苷能明显改善高脂饮食诱导的斑马鱼肝脏脂质积累和肝脏组织细胞排列松散及空泡化现象;与模型组相比,两种化合物均能降低TG、TC、LDL-c并提升HDL-c水平,异夏佛塔苷改善效果更为显著。其作用机制可能与下调脂肪酸合成基因SREBF1和FASN的表达、提高胆固醇代谢相关基因RORα的表达有关。The aim of this paper is to isolate flavonoids from Elymus nutans Griseb.and to investigate their effects on lipid metabolism in hyperlipidemia zebrafish induced by high-fat diet.Medium-pressure and high-pressure liquid chromatography combined with two-dimensional liquid chromatography were used for the isolation and purification of the compounds.The structures of the compounds were identified using nuclear magnetic resonance spectroscopy(NMR)and mass spectrometry(MS).A hyperlipidemia model of juvenile zebrafish induced by high-fat diet was established.After continuous feeding of each compound for 5 days,changes in the survival rates,body weights,lengths,and BMI of zebrafish larvae in each group were detected.Oil-red O staining and HE staining were respectively used to observe changes in lipid accumulations and histopathology.Biochemical kits were used to determine total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-c),and high-density lipoprotein cholesterol(HDL-c).Real-time fluorescence quantitative PCR(qRT PCR)was used to detect changes in the expression of lipid metabolism-related mRNA.The results show that,two flavonoids isolated from E.nutans Griseb.were identified as schaftoside and isoschaftoside,which were a pair of isomers.Both schaftoside and isoschaftoside significantly relieved high-fat diet induced liver lipid accumulation and the loosening of liver cell arrangement and vacuolization in zebrafish.Compared with the model group,schaftoside and isoschaftoside reduced the content of TG,TC,LDL-c,and increased the content of HDL-c,with the improvement effect of isoschaftoside being more significant.The mechanism of isoschaftoside may be related to down-regulating the expression of fatty acid synthesis genes SREBF1 and FASN,and increasing the expression of cholesterol metabolism-related genes RORα.

关 键 词：中高压液相色谱 夏佛塔苷 异夏佛塔苷 斑马鱼 高脂血症 

分 类 号：R285.5[医药卫生—中药学]