基于转录组学和斑马鱼模型研究BP1的神经内分泌毒性  

Study of Neuroendocrine Toxicity of 2,4-dihydroxybenzophenone Based on Transcriptomics and Zebrafish Model

作　　者：姜鑫 刘思远 宋扬[2] 靳梦 董小雷[2] Jiang Xin;Liu Siyuan;Song Yang;Jin Meng;Dong Xiaolei(Institute of Biology,Qilu University of Technology(Shandong Academy of Sciences),Key Laboratory of Drug Screening Technology,Shandong Academy of Sciences,Jinan 250103,China;School of Bioengineering,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250300,China;Shandong Provincial Key Laboratory of Molecular Engineering,School of Chemistry and Chemical Engineering,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250353,China)

机构地区：[1]齐鲁工业大学(山东省科学院)生物研究所,山东省科学院药物筛选技术重点实验室,济南250103 [2]齐鲁工业大学(山东省科学院)生物工程学院,济南250300 [3]齐鲁工业大学(山东省科学院)山东省分子工程重点实验室,化学与化工学院,济南250353

出　　处：《生态毒理学报》2023年第1期298-307,共10页Asian Journal of Ecotoxicology

基　　金：济南市“新高校20条”高校院所项目(2021GXRC106,2021GXRC111)。

摘　　要：以斑马鱼为模型,研究2,4-二羟基二苯甲酮(2,4-dihydroxybenzophenone,BP1)环境暴露对生物神经内分泌的影响。利用转录组测序技术比较空白对照组(Ctl组)与BP1处理组(2.4μg·mL^(-1)BP1)间基因表达差异,并进行GO和KEGG分析。利用野生型AB斑马鱼进行行为学检测,基于转基因斑马鱼ioz4Tg/+(AB)观察甲状腺发育情况,并通过实时荧光定量PCR检测神经内分泌相关基因表达以验证BP1的神经内分泌毒性。空白对照组与BP1处理组显著差异表达基因数为390个,GO富集分析共获得包括对刺激的反应、行为、信号和神经突触等与神经内分泌相关在内的46个条目。KEGG分析筛选出22条通路,包括信号转导、内分泌系统、信号分子与相互作用等。与空白对照组相比,BP1组运动能力限制下降,甲状腺受损。实时荧光定量PCR结果显示,与空白对照组相比,gfap、dio1、trα、trβ和tshr表达降低,gap43、dio2和tg表达升高。BP1引起斑马鱼神经内分泌毒性。The toxic effects of 2,4-dihydroxybenzophenone(BP1)on neuroendocrine in zebrafish was studied.RNA-seq was used to screen significantly differentially expressed genes between control group(Ctl group)and BP1 treatment group(2.4μg·mL^(-1)BP1),and then GO and KEGG analyses were performed.To verify the neuroendocrine toxicity of BP1,locomotion of wild-type AB zebrafish was detected,the thyroid development was ob-served based on transgenic zebrafish ioz4 Tg/+(AB),and the expression of neuroendocrine related genes were as-sayed by real-time quantitative PCR.390 significantly differentially expressed genes between the Ctl group and the BP1 group were identified.Total 46 GO items related to neuroendocrine were identified by GO enrichment analysis,including response to stimulation,behavior,signal,neural synapse,etc.KEGG analysis screened 22 pathways,including signal transduction,endocrine system,signal molecule and interaction,etc.Compared with the Ctl group,BP1 group exhibited a decreased locomotor activity and impaired development of the thyroid gland.The results of real-time quantitative PCR showed that the expression of gfap,dio1,trα,trβand tshr apparently decreased com-pared with the Ctl,while the mRNA levels of gap43,dio2 and tg significantly increased.BP1 causes neuroendo-crine toxicity in zebrafish.

关 键 词：BP1 斑马鱼 神经内分泌 转录组 

分 类 号：X171.5[环境科学与工程—环境科学]