妊娠抑制 I 型糖尿病小鼠肝脏中流出转运体的诱导。
Pregnancy represses induction of efflux transporters in livers of type I diabetic mice.
机构信息
Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, New Jersey, USA.
出版信息
Pharm Res. 2013 Sep;30(9):2209-20. doi: 10.1007/s11095-013-0981-z. Epub 2013 Jan 15.
Abstract
PURPOSE
To determine whether down-regulation of transcription factor signaling during pregnancy disrupts the induction of efflux transporters in type I diabetic mice.
METHODS
Type I diabetes was induced in female C57BL/6 mice with multiple low dose intraperitoneal injections of streptozotocin (STZ) at least 2 weeks prior to mating with normoglycemic male mice. On gestation day 14, livers were collected from vehicle- and STZ-treated non-pregnant and pregnant mice for quantification of efflux transporter and transcription factor signaling.
RESULTS
STZ treatment up-regulated expression of Mrp1-5, Mdr1, Abcg5, Abcg8, Bcrp, and Bsep mRNA and/or protein in the livers of non-pregnant mice. Interestingly, little to no change in transporter expression was observed in STZ-treated pregnant mice compared to vehicle- and STZ-treated non-pregnant mice.
CONCLUSIONS
This study demonstrates the opposing regulation of hepatobiliary efflux transporters in response to diabetes and pregnancy and points to PPARγ, Nrf2, and FXR as candidate pathways underlying the differential expression of transporters.
摘要
目的
确定妊娠期间转录因子信号下调是否会破坏 I 型糖尿病小鼠中流出转运体的诱导。
方法
至少在与正常血糖雄性小鼠交配前 2 周，用链脲佐菌素（STZ）多次腹腔内注射诱导雌性 C57BL/6 小鼠发生 I 型糖尿病。在妊娠第 14 天，从 vehicle 和 STZ 处理的非妊娠和妊娠小鼠中收集肝脏，用于定量测定流出转运体和转录因子信号。
结果
STZ 处理上调了非妊娠小鼠肝脏中 Mrp1-5、Mdr1、Abcg5、Abcg8、Bcrp 和 Bsep mRNA 和/或蛋白的表达。有趣的是，与 vehicle 和 STZ 处理的非妊娠小鼠相比，STZ 处理的妊娠小鼠中转运体的表达几乎没有变化。
结论
这项研究表明，肝脏流出转运体对糖尿病和妊娠的反应存在相反的调节，并指出 PPARγ、Nrf2 和 FXR 是转运体差异表达的候选途径。
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