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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

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

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【作者】 朱攀孙智杨波薛银刚施华宏

【Author】 ZHU Pan1,SUN Zhi1,YANG Bo1, XUE Yin-gang2,SHI Hua-hong3,(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)

【机构】 华东师范大学资源与环境学院环境科学系常州市环境监测中心华东师范大学河口海岸学国家重点实验室

【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1~500μg/L的HX531对原肠胚时期的热带爪蟾胚胎(即NF11~12阶段)进行48h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,400μg/L暴露组的胚胎存活率降低了83%(P<0.01),而500μg/L暴露组的胚胎存活率降低了97%。HX531对爪蟾胚胎48h的半数致死浓度(LC)为352μg/L。200~500μg/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50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48h对热带爪蟾胚胎的半效应浓度(EC50)为79μg/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。

【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.

【关键词】 维甲酸X受体热带爪蟾胚胎致畸
【Key words】 RXR antagonistXenopus tropicalisembryosteratogenesis
【基金】 国家自然科学基金项目(20877023);江苏省环境监测科研基金(1106)
  • 【文献出处】 癌变·畸变·突变 ,Carcinogenesis,Teratogenesis & Mutagenesis , 编辑部邮箱 ,2012年06期
  • 【分类号】R114
  • 【被引频次】1
  • 【下载频次】86
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