磺胺甲恶唑对斑马鱼早期生命阶段的发育毒性研究  

Developmental Toxicity of Sulfamethoxazole to Early Life Stages of Zebrafish

作　　者：赵浩丞 刘尚书 李佳欣 郑梦嫣 王泓锴 董飞龙 胡丰晓 Zhao Haocheng;Liu Shangshu;Li Jiaxin;Zheng Mengyan;Wang Hongkai;Dong Feilong;Hu Fengxiao(Institute of Oceanology,Fujian Agriculture and Forestry University,Fuzhou 350002,China;Fujian Key Laboratory of Marine Biotechnology,Fuzhou 350002,China)

机构地区：[1]福建农林大学海洋研究院,福州350002 [2]福建省海洋生物技术重点实验室,福州350002

出　　处：《生态毒理学报》2023年第1期114-123,共10页Asian Journal of Ecotoxicology

基　　金：国家自然科学基金青年项目(31702394);2021年福建省大学生创新创业计划项目(S202110389058)。

摘　　要：磺胺甲恶唑(sulfamethoxazole,SMX)作为一种广谱型抗生素,由于大量使用而在各类水体中广泛存在。为研究SMX对斑马鱼(Danio rerio)早期生命阶段的发育毒性,将3 hpf(hours post fertilization,受精后小时数)内的斑马鱼胚胎在不同浓度(空白对照:0μg·L^(-1),S4:4μg·L^(-1),S40:40μg·L^(-1),S400:400μg·L^(-1))的磺胺甲恶唑溶液中暴露至120 hpf,观察统计斑马鱼胚胎的孵化率,仔鱼的死亡率、心率、体长和畸形率等发育参数,并检测斑马鱼体内生长激素(GH)、胰岛素样生长因子(IGF-Ⅰ)含量以及GH/IGF轴相关基因转录水平的变化。结果显示,40μg·L^(-1)和400μg·L^(-1)的SMX暴露会导致斑马鱼死亡率显著升高,体长明显缩短,并且对仔鱼有明显的致畸作用(心包囊肿、脊椎弯曲和尾部畸形等)。SMX暴露对斑马鱼的孵化率未产生显著影响,但会造成胚胎/仔鱼心率下降。此外,在SMX胁迫下,仔鱼体内GH和IGF-Ⅰ水平显著升高。而基因转录分析发现,S4、S40和S400不同处理组SMX暴露下调了gh1(相对表达量:0.30倍、0.17倍和0.10倍)、ghrb(相对表达量:0.74倍、0.36倍和0.39倍)、igf1(相对表达量:0.75倍、0.23倍和0.33倍)和igf1ra(相对表达量:0.49倍、0.22倍和0.72倍)等多个GH/IGF轴相关基因的转录水平,激素水平的变化相较于基因转录水平的变化可能存在滞后性。实验结果表明,SMX暴露对斑马鱼表现出胚胎发育毒性,可能通过减缓心脏搏动以及干扰GH/IGF轴来抑制斑马鱼仔鱼的早期生长。As a broad-spectrum antibiotic,sulfamethoxazole(SMX)has been widely used and frequently detected in various water bodies.In order to study the developmental toxicity of SMX to zebrafish(Danio rerio),embryos within 3 hours after fertilization(hpf)were treated with different concentrations(CK:0μg·L^(-1),S4:4μg·L^(-1),S40:40μg·L^(-1),S400:400μg·L^(-1))of SMX solution until 120 hpf.The hatchability of zebrafish embryos,the mortality rate,heart rate,body length and malformation rate of larvae and other developmental parameters were observed.Besides,the contents of growth hormone(GH)and insulin-like growth factor(IGF-Ⅰ)and the transcriptional levels of genes involved in GH/IGF-axis in zebrafish were detected.The results showed that exposure to 40μg·L^(-1)and 400μg·L^(-1)of SMX significantly resulted in increased mortality and malformation(pericardium cyst,spinal curvature,tail deformity,etc.),and shortened body length.SMX stress exhibited no significant effects on the hatchability of zebrafish,but decreased the heart rates of embryos and larvae.In addition,under SMX exposure,the levels of GH and IGF-Ⅰin larval fish were significantly increased,while SMX exposure down-regulated the transcription of several genes along GH/IGF-axis,including gh1(0.30-,0.17-and 0.10-fold),ghrb(0.74-,0.36-and 0.39-fold),igf1(0.75-,0.23-and 0.33-fold)and igf1ra(0.49-,0.22-and 0.72-fold).It seemed that the response of hormones had a delay compared with the transcriptional change of genes.The current results indicate that SMX induces embryo developmental toxicity in zebrafish,and may inhibit the early growth of zebrafish via slowing heart beat and/or interfering with GH/IGF axis.

关 键 词：磺胺甲恶唑 斑马鱼 胚胎发育毒性 心率 畸形 生长抑制 GH/IGF轴 

分 类 号：X171.5[环境科学与工程—环境科学]