癌变·畸变·突变 ›› 2005, Vol. 17 ›› Issue (3): 183-186.doi: 10.3969/j.issn.1004-616x.2005.03.015

• 检测研究 • 上一篇    下一篇

重组人胰高血糖素类多肽的致畸毒性

于 燕;林 飞;张瑞娟;张振军;李安静   

  1. 西安交通大学医学院, 陕西 西安710061
  • 收稿日期:2004-05-12 修回日期:2004-06-28 出版日期:2005-05-30 发布日期:2005-05-30
  • 通讯作者: 于 燕

The Toxicity Study ofRecombinant Human Glucagon_like Peptide on Rats During thePeriod of Sensitive Teratogenesis

YU Yan;LIN Fei;ZHANG Rui-juan;ZHANG Zhen-jun;LI An-jing   

  1. College of Medical Science, Xi'an Jiaotong University,Xi'an
  • Received:2004-05-12 Revised:2004-06-28 Online:2005-05-30 Published:2005-05-30
  • Contact: YU Yan

摘要: 背景与目的: 通过在胚胎器官形成期连续给药,观察重组人胰高血糖素类多肽(recombinant human Glucagon_Like Peptide,rhGLP)对大鼠的胚胎毒性和致畸毒性。材料与方法: 试验采用SD种大鼠,每组妊娠鼠>16只。试验共分3个剂量组(260、130和65 μg/kg),1个阳性对照组和1个溶剂对照组。在大鼠胚胎器官形成期连续给药10 d(受孕的第6~15 d),每日颈背部皮下注射给予受试药物及生理盐水阴性对照1.0 ml/kg,阳性对照乙酰水杨酸(Aspirin,ASP)每天以10.0 ml/kg灌胃给予。在妊娠的第20 d,颈椎脱臼处死妊娠鼠。计数黄体数、胚胎的着床数、活胎数、早期死胎数(包括吸收胎)和晚期死胎数。观察胎仔性别、外观并称取体重后,将每窝1/2的活胎仔乙醇固定,2 %氢氧化钾软化,茜素红染色,甘油透明后在大视场工作仪上检查骨骼发育情况。另1/2活胎仔经Bouins液固定后,在大视场工作仪上检查内脏发育情况。 结果: 受试药物各剂量组均未显示出明显的胎仔生长发育障碍及骨骼和内脏畸形。结论: 在<260 μg/kg剂量下,重组人胰高血糖素类多肽对大鼠无胚胎毒性和致畸毒性。

关键词: 重组人胰高血糖素类多肽, 致畸敏感期毒性, 致畸毒性

Abstract: BACKGROUND & AIM: To observe whether there are embryonic and teratogenic toxicity on rats disposed by different dosages of recombinant human glucagon_like peptide(rhGLP) continuously during the period of organ formation. MATERIAL AND METHODS: The SD rats were used in this experiment. The pregnant rats were divided into five groups, three dosage groups (260,130 and 65 μg/kg), one positive and one negative control groups. There were more than 16 pregnant rats in every group. The treated groups and the negative control (normal physiological saline 1.0 ml/kg) group were injected continuously via hypodermic of back neck every day for ten days during the period of organ formation, while the positive control group was disposed via mouth by 10.0 ml/kg of aspirin. The numbers of luteal, nidation, alive_embryo, forepart fetal death, advanced stage fetal death were counted after the pregnant rats were sacrificed by disjointed cervical vertebrae at the twentieth day. After observed the sex, appearance and weight of embryonic rats, they were divided into two groups. In one group, the bone development was observed after ethanol fixing, potassium hydroxide melting, Alizarin Red staining transparencing. In another group, the viscera development was observed after Bouins solution fixing under and glycerin big_inspect_instrument. RESULTS: There were no obvious development abnormality in embryonic rats' appearances, bones and viscera in every disposed dosage groups. CONCLUSION: Recombinant glucagonant_like peptide has no embryonic and teratogenic toxicity under the dosage of 260 μg/kg.

Key words: recombinant human glucagon_like peptide, the period of sensitive teratogenesis, teratogenic toxicity