基于转录组学研究雷公藤甲素对仓鼠卵巢细胞毒性的分子机制  

Molecular mechanism of triptolide-induced toxicity to Chinese hamster ovary cells based on transcriptomics

作　　者：程坦 高宁[2] 郑晓玲 应牡英[1,3] CHENG Tan;GAO Ning;ZHENG Xiao-ling;YING Mu-ying(Queen Mary School of Nanchang Univiersity,Nanchang 330006,China;Heilongjiang University of Chinese Medicine,Harbin 150040,China;Basic Medical College of Nanchang University,Nangchang 330006,China)

机构地区：[1]南昌大学玛丽女王学院,南昌330006 [2]黑龙江中医药大学,哈尔滨150040 [3]南昌大学基础医学院,南昌330006

出　　处：《天然产物研究与开发》2021年第11期1836-1844,1968,共10页Natural Product Research and Development

基　　金：国家自然科学基金(81503271,31160233)。

摘　　要：本研究以中国仓鼠卵巢细胞系(Chinese hamster ovary cells,CHO)为模型,比较雷公藤甲素给药前后CHO细胞基因表达变化,并探讨雷公藤甲素对卵巢细胞毒性的分子机制。课题组利用HiSeq2000对样本进行转录组测序并比较雷公藤给药组与对照组间基因表达差异。随后,利用ClueGO与STRING 11分析了差异基因的生物学功能。结果表明,与对照组相比,雷公藤甲素给药组共有740条差异表达基因,其中上调基因286条,参与16个GO(Gene Ontology)生物学过程;下调基因454条,参与18个GO生物学过程。所有差异基因共涉及22条代谢与信号通路。功能分析结果显示,差异基因所涉及的GO生物学过程及代谢与信号通路中,异戊二烯代谢、形态发生、信号受体活性调节等生物学过程,以及IL-17信号通路、TNF信号通路、PI3K-Akt信号通路、胆固醇合成通路,与雷公藤甲素的卵巢细胞毒性密切相关。研究结果表明雷公藤甲素能够通过影响多种途径扰乱卵巢细胞信号转导与代谢过程,从而造成卵巢细胞损伤,产生卵巢毒性。To explore the molecular mechanism of ovarian toxicity caused by tripolide,Chinese hamster ovary cells(CHO)were treated with triptolide.Then the gene expression was sequenced by HiSeq2000,and the biological functions of differentially expressed genes(DEGs)between treatment and control groups were analyzed with ClueGO and STRING 11.Compared with the control group,there were 740 DEGs in the treatment group,286 up-regulated genes involved in 16 GO biological processes while 454 down-regulated genes involved in 18 GO biological processes.And 22 KEGG signaling/metabolic pathways were enriched.Among them,several GO processes and KEGG pathways were closely related to the ovarian toxicity of triptolide,such as isoprenoid biosynthetic process,anatomical structure morphogenesis,regulation of signaling receptor activity,IL-17 signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway and steroid biosynthesis.The results showed that triptolide can disrupt various signaling pathways and metabolic processes of ovarian cells,which causes ovarian cells damage and bring out ovarian toxicity.

关 键 词：雷公藤甲素 生殖毒性 卵巢细胞 高通量测序 

分 类 号：R285[医药卫生—中药学]