吡咯西啶双烷生物碱暴露对生长发育迟缓胎鼠肾上腺皮质酮合成功能的影响.docVIP

  吡咯西啶双烷生物碱暴露对生长发育迟缓 胎鼠肾上腺皮质酮合成功能的影响# 寇皓，郭喻，汪晖** 5 10 15 （武汉大学基础医学院药理学系,武汉 430071） 摘要：目的：从胎肾上腺甾体合成功能改变的角度探讨吡咯西啶双烷生物碱（PAs）所致发 育毒性。方法：小鼠孕中晚期给予野百合碱（Mct）或倒千里光碱（Ret），记录胎鼠体重， 观察母血/胎血皮质酮（CORT）和促肾上腺皮质激素（ACTH）含量变化，检测胎盘 II 型 11β-羟类固醇脱氢酶（11β-HSD-2）、胎肾上腺细胞色素 P450（CYP）11A1 和甾体激素 合成急性调节蛋白（StAR）及 CYP3A16 表达情况。结果：与正常对照组相比，Mct 和 Ret 能降低胎鼠体重（P0.01, P0.05），升高胎血 CORT 水平（P0.05）。Mct 组母血 CORT 有升高趋势且 11β-HSD-2 表达降低；Ret 组胎盘 11β-HSD-2 的 mRNA 表达呈现升高趋势， CYP11A1 和 StAR 的 mRNA 和蛋白表达有升高趋势或明显升高（P0.05）。Mct 组 CYP3A16 的 mRNA 表达显著降低（P0.05），Ret 组亦有下降趋势。结论：孕期 Mct 或 Ret 处理小鼠 均可引起胎鼠发育毒性，其共性机制可能与胎血 CORT 增高有关。Mct 的影响可能是母源性 CORT 进入胎儿所致，而 Ret 则主要通过 StAR 介导的胎肾上腺自身 CORT 合成增强有关。 关键词：毒理学；野百合碱；倒千里光碱；糖皮质激素；胎肾上腺 中图分类号：R99 20 Effects of pyrrolizidine alkaloids on the function of adrenal steroidogenesis in intrauterine growth-retarded mice KOU Hao, GUO Yu, WANG Hui (Department of Pharmacology, Basic Medical School, Wuhan University, Wuhan 430071) 25 30 35 40 Abstract: Objectives: to investigate the pyrrolizidine alkaloids (PAs)-induced developmental toxicities from the perspective of adrenal steroidogenic function. Methods: Pregnant mice were administered with monocrotaline (Mct) or retrorsine (Ret) during second and third trimesters. The fetuses were weighed. The level of corticosterone (CORT) in maternal and fetal serum as well as fetal adrenocorticotropic hormone (ACTH) were detected. The expression of placental 11β -hydroxysteroid dehydrogenase type 2 (11β-HSD-2), adrenal cytochrome P450 (CYP) 11A1 and steroidogenic acute regulatory protein (StAR) as well as CYP3A16 were measured. Results: When compared with control, Mct and Ret significantly reduced the fetal body weight (P0.01, P0.05) while elevated the fetal CORT level (P0.05). The level of maternal serum CORT in Mct group had an increased tendency that the expression of placental 11?-HSD-2 was likely to be decreased. For Ret group, the 11?-HSD-2 mRNA expression had an increased tendency while both adrenal CYP11A1 and StAR expression showed elevated ten