夏敏杰, 王玉柱, 田芳, 缪建成, 杨威, 杨明俊, 丁训城, 李卫华, 王晓东, 胡晶莹. 维甲酸诱导SD大鼠胚胎骨骼畸形的图像分析[J]. 环境与职业医学, 2018, 35(9): 795-800. DOI: 10.13213/j.cnki.jeom.2018.18134
引用本文: 夏敏杰, 王玉柱, 田芳, 缪建成, 杨威, 杨明俊, 丁训城, 李卫华, 王晓东, 胡晶莹. 维甲酸诱导SD大鼠胚胎骨骼畸形的图像分析[J]. 环境与职业医学, 2018, 35(9): 795-800. DOI: 10.13213/j.cnki.jeom.2018.18134
XIA Min-jie, WANG Yu-zhu, TIAN Fang, MIAO Jian-cheng, YANG Wei, YANG Ming-jun, DING Xun-cheng, LI Weihua, WANG Xiao-dong, HU Jing-ying. Image analysis on skeletal malformation in SD rat embyros induced by retinoic acid[J]. Journal of Environmental and Occupational Medicine, 2018, 35(9): 795-800. DOI: 10.13213/j.cnki.jeom.2018.18134
Citation: XIA Min-jie, WANG Yu-zhu, TIAN Fang, MIAO Jian-cheng, YANG Wei, YANG Ming-jun, DING Xun-cheng, LI Weihua, WANG Xiao-dong, HU Jing-ying. Image analysis on skeletal malformation in SD rat embyros induced by retinoic acid[J]. Journal of Environmental and Occupational Medicine, 2018, 35(9): 795-800. DOI: 10.13213/j.cnki.jeom.2018.18134

维甲酸诱导SD大鼠胚胎骨骼畸形的图像分析

Image analysis on skeletal malformation in SD rat embyros induced by retinoic acid

  • 摘要: 目的 运用维甲酸诱导大鼠胚胎畸形模型,探索维甲酸诱导大鼠胚胎畸形的剂量反应关系,为实验动物发育毒理学畸形解剖图像(DevTox)数据库补充大鼠胚胎骨骼畸形图片数据。

    方法 将SD大鼠孕鼠随机分为4组,即对照组、50、100、150 mg/kg维甲酸组。各组在孕第10天灌胃给药1次,孕第20天处死孕鼠,取出胚胎,观察记录各组胚胎总数与发育情况。胚胎骨骼经茜素红染色,观察胚胎各部位骨骼畸形及发生率,并在解剖镜下摄取畸形图片。

    结果 50 mg/kg及以上剂量组的维甲酸可诱导SD大鼠胚胎骨骼出现明显的多发性畸形,致畸率可达100%,畸形主要表现为下颌骨缺失、上颌骨与颧弓融合;胸骨节缺失;第10~13节胸椎融合、缺失;腰椎融合、缺失;骨盆带骨骼与尾椎缺失等。维甲酸各组骨骼畸形的表型和畸形发生率呈现出高度的一致性和可重复性,三个剂量组间的胚胎畸形率均为100%,但畸形程度随剂量增高而加重。收集的正常与畸形的图片清晰,无气泡、反光干扰,且分辨率较高。

    结论 50 mg/kg及以上维甲酸在孕第10天灌胃给药,对SD大鼠胚胎骨骼有明显的致畸作用,致畸率高,且畸形类型多样。实验所得骨骼畸形图片可上传DevTox数据库,补充丰富该数据库内容。

     

    Abstract: Objective To supplement the DevTox database with various embryonic skeletal malformation images of SD rats by constructing a rat model using retinoic acid (RA) and assessing the dose-response relationship between RA and malformation

    Methods Pregnant SD rats were administered via gavage on gestational day (GD) 10 with RA at doses of 50, 100, and 150 mg/kg or with corn oil. After the animals were executed on GD 20, the details of embryo implantation and development in each group were observed and recorded. After embryo bones were stained by alizarin red for identifying skeletal malformation in each body part, the incidence of bone deformity was calculated and the identified malformation site images were taken under anatomical microscope.

    Results Multiple abnormalities in embryo bones were clearly observed in all three RA-treated groups with teratogenetic rates up to 100%. The main abnormalities included dagnathia, fusion of maxilla and zygomatic arch, sternothyma, deficiency or fusion of thoracic vertebra section 10-13, deficiency or fusion of lumbar vertebra, deficiency of pelvic girdle and caudal vertebra. The phenotype and occurrence rate of abnormalities in the three RA-treated groups were highly consistent and repeatable, the rates of embryo abnormalities among the three dose groups were all 100%, but the degrees of abnormalities increased with higher doses. The collected images of normal and abnormal bones were clear and free from bubbles and reflections with high resolution.

    Conclusion Severe skeletal malformations are identified in SD rat embryos after maternal exposure to RA on GD10 at 50 mg/kg and above, showing a high malformation rate and various abnormality types. The images of skeletal malformation could supplement the DevTox database.

     

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