手性杀虫剂氟氯菊酯对小鼠内分泌系统干扰差异研究

发布时间：2018-06-11 20:00

本文选题：顺式-氟氯菊酯 + 手性　；参考：《浙江工业大学》2013年硕士论文

【摘要】：作为一种手性合成拟除虫菊酯类农药,氟氯菊酯(BF)在世界上被广泛应用于控制农田与居室里的害虫。目前,商业在售的氟氯菊酯包涵两种对映体,分别是1R-cis-BF和1S-cis-BF。在本研究中,我们将顺式-氟氯菊酯(cis-BF)拆分成了这两种对映体,分别对不同发育阶段的小鼠进行暴露,探讨两者之间的内分泌干扰差异。在第一部分实验中,四周龄雄性ICR小鼠分别口服暴露于7.5和15 mg/kg/day的cis-BF, 1R-cis-BF和1S-cis-BF3周,对照组喂普通饲料。研究结果显示小鼠睾丸中胆固醇合成、转运和睾酮合成相关基因的转录水平受到cis-BF的影响。我们还发现睾酮合成通路上的几个关键基因如P450scc和P450-17α的转录水平在1S-cis-BF对映体处理组中显著的降低,同时1S-cis-BF处理组血清中的睾酮浓度也显著降低。以上的研究结果说明对青春发育期小鼠暴露时,两种cis-BF对映体都对小鼠有内分泌干扰效应,并且1S-cis-BF比1R-cis-BF的内分泌干扰毒性要大。在第二部分实验中,母鼠分别在怀孕前3周和怀孕期口服暴露15mg/kg/day的1R-cis-BF和1S-cis-BF(约3周)。母鼠怀孕期暴露1S-cis-BF显著减少3周龄和6周龄雄性子鼠睾丸中PBR和StAR基因的转录,同时在6周龄雄性子鼠睾丸中P450-17α的mRNA水平也显著降低。母鼠怀孕前或怀孕期暴露1S-cis-BF显著减少6周龄雄性子鼠睾丸中SRB1和P450scc基因的转录。因此,研究结果显示母鼠口服暴露3周cis-BF,尤其是怀孕期暴露,会造成其雄性子鼠的内分泌干扰,而且1S-cis-BF比1R-cis-BF的内分泌干扰毒性要大。这些数据有助于我们在对映体水平上理解cis-BF对哺乳动物的内分泌干扰效应。
[Abstract]:As a chiral synthetic pyrethroid pesticide, permethrin (BF) has been widely used in the control of pests in farmland and house. At present, the commercially available permethrin contains two enantiomers, 1R-cis-BF and 1S-cis-BF. In this study, we split cis-permethrin cis-BF into these two enantiomers and exposed mice at different developmental stages to explore the difference of endocrine disruptions between them. In the first part, four week-old male ICR mice were exposed to 7.5 and 15 mg/kg/day cis-BFs, 1R-cis-BF and 1S-cis-BF3 weeks, respectively. The results showed that the transcription level of genes related to cholesterol synthesis, transport and testosterone synthesis was affected by cis-BF. We also found that the transcriptional levels of several key genes in the testosterone synthesis pathway, such as P450 SCC and P450-17 伪, decreased significantly in the 1S-cis-BF enantiomer treatment group and the serum testosterone concentration in the 1S-cis-BF treatment group. The above results suggest that both cis-BF enantiomers have endocrine disrupting effects on mice when exposed to pubertal mice, and 1S-cis-BF is more toxic than 1R-cis-BF. In the second part of the experiment, the female rats were exposed to 1R-cis-BF and 1S-cis-BFof (about 3 weeks) of 15mg/kg/day before 3 weeks of pregnancy and during pregnancy respectively. During pregnancy, 1S-cis-BF significantly decreased the transcription of PBR and star gene in the testis of 3-week-old and 6-week-old male offspring, and the mRNA level of P450-17 伪 in the testis of 6-week-old male offspring. Exposure to 1S-cis-BF significantly reduced the transcription of SRB1 and P450 SCC genes in the testis of 6-week-old male offspring rats before or during pregnancy. Therefore, the results showed that oral exposure to cis-BF for 3 weeks, especially during pregnancy, caused endocrine disruptions in male offspring, and 1S-cis-BF was more toxic than 1R-cis-BF. These data help us to understand the endocrine disrupting effects of cis-BF on mammals at enantiomeric level.
【学位授予单位】：浙江工业大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R114

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