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通过离体灌注鉴定和量化金工程纳米材料,并研究其对大鼠胎盘跨膜液体转运的影响。

Identification and quantification of gold engineered nanomaterials and impaired fluid transfer across the rat placenta via ex vivo perfusion.

机构信息

Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, 160 Frelinghuysen Rd., Piscataway, NJ 08854, USA.

Environmental and Occupational Health Sciences Institute, 170 Frelinghuysen Rd., Piscataway, NJ 08854, USA.

出版信息

Biomed Pharmacother. 2019 Sep;117:109148. doi: 10.1016/j.biopha.2019.109148. Epub 2019 Jul 4.

Abstract

Development and implementation of products incorporating nanoparticles are occurring at a rapid pace. These particles are widely utilized in domestic, occupational, and biomedical applications. Currently, it is unclear if pregnant women will be able to take advantage of the potential biomedical nanoproducts out of concerns associated with placental transfer and fetal interactions. We recently developed an ex vivo rat placental perfusion technique to allow for the evaluation of xenobiotic transfer and placental physiological perturbations. In this study, a segment of the uterine horn and associated placenta was isolated from pregnant (gestational day 20) Sprague-Dawley rats and placed into a modified pressure myography vessel chamber. The proximal and distal ends of the maternal uterine artery and the vessels of the umbilical cord were cannulated, secured, and perfused with physiological salt solution (PSS). The proximal uterine artery and umbilical artery were pressurized at 80 mmHg and 50 mmHg, respectively, to allow countercurrent flow through the placenta. After equilibration, a single 900 μL bolus dose of 20 nm gold engineered nanoparticles (Au-ENM) was introduced into the proximal maternal artery. Distal uterine and umbilical vein effluents were collected every 10 min for 180 min to measure placental fluid dynamics. The quantification of Au-ENM transfer was conducted via inductively coupled plasma mass spectrometry (ICP-MS). Overall, we were able to measure Au-ENM within uterine and umbilical effluent with 20 min of material infusion. This novel methodology may be widely incorporated into studies of pharmacology, toxicology, and placental physiology.

摘要

纳米颗粒产品的开发和应用正在迅速发展。这些颗粒广泛应用于家庭、职业和生物医学领域。目前,尚不清楚孕妇是否能够利用潜在的生物医学纳米产品,因为这涉及到胎盘转移和胎儿相互作用的问题。我们最近开发了一种离体大鼠胎盘灌注技术,以评估外源性物质的转移和胎盘的生理变化。在这项研究中,从妊娠(妊娠第 20 天)的 Sprague-Dawley 大鼠中分离出一段子宫角和相关胎盘,并将其放置在改良的压力肌动描记器室中。用套管分别插入子宫动脉近段和远段及脐带血管,并固定,用生理盐水(PSS)灌流。子宫动脉近段和脐动脉分别加压至 80mmHg 和 50mmHg,以允许胎盘内的逆流。平衡后,将 900μL 的 20nm 金纳米工程颗粒(Au-ENM)单次推注到近段母动脉。每隔 10 分钟收集一次远端子宫和脐静脉的流出液,共 180 分钟,以测量胎盘的流体动力学。通过电感耦合等离子体质谱(ICP-MS)来定量 Au-ENM 的转移。总的来说,我们能够在 20 分钟的材料输注后测量子宫和脐静脉流出液中的 Au-ENM。这种新方法可能广泛应用于药理学、毒理学和胎盘生理学的研究。

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