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

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。

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.