摘要
本研究旨在通过转录组测序技术及联合代谢组学数据分析,探讨肉苁蓉总苷(Glycosides of Cistanche, GCs)发挥拟雌激素作用机制。试验以性未成熟的雌性SD大鼠(视为雌激素水平为零)为模型、分为模型对照组、己烯雌酚对照组、GCs给药组,另设正常成年雌性SD大鼠对照组。各组灌胃生理盐水或等体积药物,早、晚各一次,给药均持续3 d。各组随机取子宫组织进行RNA-Seq转录组测序,并对转录组测序数据和试验前期靶向代谢组学数据进行联合分析,从转录水平和内源性代谢物水平共同揭示GCs拟雌激素作用的机制。结果表明,通过RNA-Seq测序发现,GCs发挥拟雌激素作用调控的关键基因有46个,主要参与的生物过程为雌激素反应、氮化合物代谢过程的正向调控、发育过程、生物过程的正向调节等;主要参与的信号通路为雌激素信号通路、cAMP信号通路、Rap1信号通路、MAPK信号通路等。联合分析表明,代谢组与转录组共有通路16条,DEGs与DEMs相关性分析表明,牛磺酸及Gad2、Gad1、Ggt1、Ggt5、Cdo1;柠檬酸及Gldc;鸟氨酸与Pycrl、Pycr1;脯氨酸与Ckmt1、Sat1、Pycr1、Pycrl、Aoc1;-酮戊二酸与Pdha1l1、Ogdhl是GCs拟雌激素作用的关键候选代谢物及候选基因。GCs发挥拟雌激素作用调控的关键基因有46个,主要参与的信号通路为雌激素信号通路、cAMP信号通路、Rap1信号通路、MAPK信号通路等。牛磺酸及Gad2、Gad1、Ggt1、Ggt5、Cdo1;柠檬酸及Gldc;鸟氨酸与Pycrl、Pycr1;脯氨酸与Ckmt1、Sat1、Pycr1、Pycrl、Aoc1;-酮戊二酸与Pdha1l1、Ogdhl是GCs拟雌激素作用的关键候选代谢物及候选基因。本研究为肉苁蓉总苷拟雌激素作用机制提供了新思路。
The purpose of this study was to analyze transcriptome sequencing technology and combined metabolomics data,the possible mechanismof estrogen-like effects of Glycosides of Cistanche(GCs)was investigated.Sexually immature female SDrats(regarded as zero estrogen level)were used as the model,divided into model control group,diethylstilbestrol control group,GCs administration group,and normal adult female SD rats control group.Each group was given intragastric administration of normal saline or equal-volume drug,once in the morning and once in the evening,and the administration lasted for 3 days.Uterus tissues were randomly taken from each group for RNA-Seq transcriptome sequencing,and the transcriptome sequencing data and the targeted metabolomics data of the research group were jointly analyzed,so as to jointly reveal the mechanismof GCs estrogen-like effect fromthe transcriptional level and endogenous metabolite level.The results showed that 46 key genes of GCs were identified by RNA-Seq sequencing,which were mainly involved in the positive regulation of estrogen response,nitrogen metabolism,development and biological processes.The main signaling pathways involved are es-trogen signaling pathway,cAMP signaling pathway,Rap1 signaling pathway,MAPKsignaling pathway,etc.The combined analysis showed that themetabolome and transcriptome had 16 common pathways,and the correlation analysis between DEGs and DEMs showed that taurine was involved in the development of dems,including Gad2,Gad1,Ggt1,Ggt5,and Cdo1.Citric acid and Gldc;Ornithine and Pycrl,Pycr1;Proline and Ckmt1,Sat1,Pycr1,Pycrl,Aoc1;-ketoglutaric acid,Pdha1l1 and Ogdhl are the key candidate metabolites and candidate genes for the estrogen-like effect of GCs.There are 46 key genes involved in the regulation of GCs,which aremainly involved in estrogen signaling pathway,cAMP signaling pathway,Rap1 signaling pathway,MAPK signaling pathway,etc.Taurine and Gad2,Gad1,Ggt1,Ggt5,Cdo1;Citric acid and Gldc;Ornithine and Pycrl,Pycr1;Proline and Ckmt1,Sat1,Pycr1,Pycrl,Aoc1;-ketoglutaric acid,Pdha1l1 and Ogdhl are the key candidate metabolites and candidate genes for the estrogen-like effect of GCs.This study provides a new way to further study the estrogen-like mechanismof total cistanche glycosides.
作者
宋辉
单文猜
黄晓俏
王玉涵
韩栩楠
谷天姝
SONG Hui;SHAN Wencai;HUANG Xiaoqiao;WANG Yuhan;HAN Xunan;GU Tianshu(Pharmaceutical Engineering Technology Research Center,Harbin University of Commerce,Harbin 150076,China)
出处
《特产研究》
2025年第3期7-16,26,共11页
Special Wild Economic Animal and Plant Research
基金
哈尔滨市科技计划项目(2015RQQXJ091)
黑龙江省博士后项目(LBH-Z20023)
哈尔滨商业大学产业化项目(22CZ17)。
关键词
肉苁蓉总苷
拟雌激素
转录组学
代谢组学
联合分析
Glycosides of Cistanche deserticola
estromimetic
transcriptomics
metabolomics
joint analysis
