【作者】 于淼； 张晓娜； 郭琳琳； 田华； 王蔚； 汝少国；

【Author】 Miao Yu;Xiaona Zhang;Linlin Guo;Hua Tian;Wei Wang;Shaoguo Ru;College of Marine Life Sciences, Ocean University of China;

【机构】 中国海洋大学海洋生命学院；

【摘要】 氨基脲是水产养殖兽药呋喃西林的主要代谢产物,具有多种毒性效应。已有研究表明,氨基脲暴露可抑制雌性斑马鱼卵黄原蛋白以及雌激素受体的转录,具有抗雌激素效应。为进一步探讨氨基脲的抗雌激素效应机制,本研究采用半静态暴露实验,以1¹000μg/L的氨基脲暴露性成熟的雌性斑马鱼96h和28d,采用酶联免疫的方法检测了雌鱼血浆中17β-雌二醇（E₂）水平,用实时定量PCR的方法检测了生殖轴线中的相关基因、γ-氨基丁酸支路相关酶基因、瘦素基因的转录水平,同时观察了卵巢的显微结构。研究结果表明氨基脲暴露96h及28d后,血浆E₂水平明显下降,卵巢中卵母细胞的成熟度降低,说明氨基脲是通过降低生物体内源E₂水平来发挥其抗雌激素效应的。而氨基脲导致E₂水平降低则与生殖轴线中关键基因的转录水平显著下调有关。此外氨基脲对γ-氨基丁酸合成的抑制以及对瘦素基因转录的激活也是导致E₂水平降低的重要因素。本研究的结果为具有氨基脲类似毒性的物质开展抗雌激素效应机制研究提供了一个新的借鉴。更多还原

【Abstract】 Semicarbazide（SMC）, the marker residue for the banned veterinary antibiotic used in aquaculture, has various toxic effects. It was reported SMC exposure inhibited the transcription of hepatic vitellogenin and estrogen receptors in female zebrafish（Danio rerio）, suggesting that it had anti-estrogenic properties. In order to elucidate the mechanisms underlying these, we exposed female zebrafish to SMC and used enzyme-linked immunosorbent assays to examine plasma17β-estradiol（E₂） levels. Gonad histology was analyzed and the mRNA expression of genes involved in the reproductive axis, the γ-aminobutyric acid（GABA） shunt, and leptin was quantified by real-time PCR. Zebrafish were exposed to 1¹000 μg/L SMC in a semi-static system for 96 hours or 28 days. Plasma E₂ levels were significantly decreased and ovarian maturation was inhibited by SMC, suggesting that its anti-estrogenic effect was exerted by reducing endogenous E₂ levels. This was likely due to the general depression of the gene transcriptional levels along the reproductive axis. In addition, SMC-mediated inhibition of GABA synthesis and stimulation of leptin gene transcription made contributions to the decrease of plasma E₂ levels更多还原