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维甲酸X受体抑制剂HX531对热带爪蟾胚胎的致畸效应

朱 攀1 /孙 智1/杨 波1/薛银刚2/施华宏3,*   

  1. 1. 华东师范大学资源与环境学院环境科学系,上海 200062;2. 常州市环境监测中心,江苏 常州 213001;3. 华东师范大学河口
    海岸学国家重点实验室,上海 200062
  • 收稿日期:2012-04-09 修回日期:2012-10-09 出版日期:2011-11-30 发布日期:2011-11-30
  • 通讯作者: 施华宏, E-mail:hhshi@des.ecnu.edu.cn
  • 作者简介:朱 攀(1987- ),女,硕士,研究方向:生态毒理学。E-mail: zhupan2006cxzx@126.com
  • 基金资助:

    国家自然科学基金项目(20877023) ;江苏省环境监测科研基金(1106)

Teratogenic effects of retinoid X receptor antagonist HX531 on Xenopus tropicalis embryos

ZHU Pan1,SUN Zhi1,YANG Bo1,XUE Yin-gang2,SHI Hua-hong3,*   

  1. 1. Department of Environmental Science, East China Normal University, Shanghai 200062; 2. Changzhou Environmental Monitoring Center, Changzhou 213001, Jiangsu; 3. State Key Laboratory of Estuarine and Coastal Research, East China Normal University, Shanghai 200062, China
  • Received:2012-04-09 Revised:2012-10-09 Online:2011-11-30 Published:2011-11-30
  • Contact: SHI Hua-hong, E-mail:hhshi@des.ecnu.edu.cn
  • About author:朱 攀(1987- ),女,硕士,研究方向:生态毒理学。E-mail: zhupan2006cxzx@126.com
  • Supported by:

    国家自然科学基金项目(20877023) ;江苏省环境监测科研基金(1106)

摘要:

目的: 研究维甲酸X受体抑制剂HX531对热带爪蟾(Xenopus tropicalis)胚胎的致畸效应。 方法:用1~500 μg/L的HX531对原肠胚时期的热带爪蟾胚胎(即NF11~12阶段)进行48 h暴露,观测胚胎存活、生长及畸形等指标。 结果:与对照组存活率(100%) 相比,400 μg/L暴露组的胚胎存活率降低了83%(P<0.01),而500 μg/L暴露组的胚胎存活率降低了97%。HX531对爪蟾胚胎48 h的半数致死浓度 (LC50)为352 μg/L。200~500 μg/L暴露组的胚胎体长比对照组减少了18.4%~41.1%(P<0.01),并且各浓度组的总畸形率均达100%(P<0.01),引起的主要畸形表型为眼睛异常、脑缩小、肠道异常、泄殖腔突出、围心腔水肿和鳍减少或消失等。HX531暴露48 h对热带爪蟾胚胎的半效应浓度 (EC50)为79 μg/L,致畸指数为4.4。 结论:维甲酸X受体受体抑制剂HX531对热带爪蟾胚胎具有极强的致畸效应,表明维甲酸X受体在爪蟾胚胎发育过程中有重要作用。

关键词: 维甲酸X受体, 热带爪蟾, 胚胎, 致畸

Abstract:

OBJECTIVE:  To investigate the teratogenic effects of HX531 on Xenopus tropicalis embryos. METHODS:Xenopus tropicalis embryos were exposed to 1-500 μg/L HX531 for 48 h. The percentages of survival,body length and malformations were measured. RESULTS:HX531 decreased the survival of embryos by 83% at the concentration of 400 μg/L and by 97% at the concentration of 500 μg/L. The half lethal concentration (LC50) of HX531 at 48 h was 352 μg/L. The body length of embryos decreased by 18.4%-41.1% in 200-500 μg/L HX531-treated groups. After 48 h of exposure,the total percentages of malformations significantly increased and reached 100% in 200-500 μg/L HX531-treated groups. HX531 also led to multiple abnormal phenotypes,including abnormal brains and eyes,narrow fins,pericardial edema and bent tails. The half-maximal effective concentration (EC50) at 48 h was 79 μg/L and the teratogenic index was 4.4. CONCLUSION:HX531 was a strong teratogen and that RXR played an important role in the development of vertebrate embryos.