龚华云, 朱勇, 李宗河, 范小艳, 樊荣, 王昉彤. 新型PPAR-δ激动剂对大鼠胚胎-胎仔发育毒性的研究J. 药学学报, 2014,49(11): 1536-1542.
引用本文: 龚华云, 朱勇, 李宗河, 范小艳, 樊荣, 王昉彤. 新型PPAR-δ激动剂对大鼠胚胎-胎仔发育毒性的研究J. 药学学报, 2014,49(11): 1536-1542.
GONG Hua-yun, ZHU Yong, LI Zong-he, FAN Xiao-yan, FAN Rong, WANG Fang-tong. Embryo-fetus development toxicity of a novel PPAR-δ agonist in ratJ. Acta Pharmaceutica Sinica, 2014,49(11): 1536-1542.
Citation: GONG Hua-yun, ZHU Yong, LI Zong-he, FAN Xiao-yan, FAN Rong, WANG Fang-tong. Embryo-fetus development toxicity of a novel PPAR-δ agonist in ratJ. Acta Pharmaceutica Sinica, 2014,49(11): 1536-1542.

新型PPAR-δ激动剂对大鼠胚胎-胎仔发育毒性的研究

Embryo-fetus development toxicity of a novel PPAR-δ agonist in rat

  • 摘要: 考察新型PPAR-δ激动剂HS060098对SD大鼠胚胎-胎仔毒性。将SD孕鼠随机分为溶剂对照组和低、中、高等3个剂量组, 大鼠妊娠6~15天(GD6-15)分别口服灌胃1% 羟丙基甲基纤维素水溶液和10、30、100 mg·kg-1·d-1剂量的HS060098混悬液。GD20处死孕鼠, 计数母体动物黄体数、着床数, 观察胚胎生存死亡情况; 检查生存胎仔的体重、性别、外观、内脏及骨骼等指标。结果显示, 各给药组孕鼠临床症状及胎仔外观、内脏未见明显异常, 但100 mg·kg-1·d-1剂量组的孕鼠体重增长缓慢(P < 0.01)且胎仔骨骼骨化延迟(P < 0.01), 30 mg·kg-1·d-1剂量组第二胸骨节骨化不全的胎仔数和窝数均明显高于溶剂对照组(P < 0.05), 各给药组胎仔均有骨骼畸形发生。结果提示, 在本实验室条件下新型PPAR-δ激动剂HS060098对SD妊娠大鼠有一定母体毒性, 对胎仔骨骼发育有不良影响。

     

    Abstract: The study aims to investigate the embryo-fetus development toxicity of the novel PPAR-δ agonist HS060098 on SD rats. The pregnant rats that were randomly divided into the solvent control group(1% hydroxypropyl methyl cellulose water solution)and HS060098 suspension groups(10, 30 and 100 mg·kg-1·d-1)were orally administered with HS060098 suspension or vehicle during the gestation of 6-15 days(GD6-15). At termination(GD20), female rats were sacrificed. The pregnant females were evaluated by corpora lutea count, implantation sites, existence and death of embryos. Fetal sex, weight, externals, variations and malformations of viscus and skeleton were observed. The results show that there were no significant abnormality in maternal general conditions and fetal appearance as well as viscera, but in the 100 mg·kg-1·d-1 group, the maternal weight gain decreased greatly(P < 0.01)and the skeletal ossification delayed remarkably(P < 0.01); in the 30 mg·kg-1·d-1 group, the fatal and litter number of incompletely ossified sternebrae Ⅱ was higher than those of the control group(P < 0.05); the skeletal malformations occurred in all dose groups, which indicate that the novel PPAR-δ agonist HS060098 had maternal toxicity and adversely effected fetal skeletal development under the experimental conditions.

     

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