Micurova Andrea, Kluknavsky Michal, Liskova Silvia, Balis Peter, Skratek Martin, Okruhlicova Ludmila, Manka Jan, Bernatova Iveta
Centre of Experimental Medicine, Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, 813 71 Bratislava, Slovakia.
Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia.
Biomedicines. 2021 Dec 7;9(12):1855. doi: 10.3390/biomedicines9121855.
We investigate the distribution and biological effects of polyethylene glycol (PEG)-coated magnetite (FeO@PEG) nanoparticles (~30 nm core size, ~51 nm hydrodynamic size, 2 mg Fe/kg/day, intravenously, for two days) in the aorta and liver of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). FeO@PEG had no effect on open-field behaviour but reduced the blood pressure (BP) of FeO@PEG-treated SHR (SHRu) significantly, compared to both FeO@PEG-treated WKY (WKYu) and saline-treated control SHR (SHRc). The FeO@PEG content was significantly elevated in the aorta and liver of SHRu vs. WKYu. Nitric oxide synthase (NOS) activity was unaltered in the aorta, but significantly increased in the liver of SHRu vs. SHRc. In the aorta, FeO@PEG treatment increased , and gene expression (considered main effects). In the liver, FeO@PEG significantly elevated and gene expression in SHRu vs. SHRc, as well as and gene expression (considered main effects). Noradrenaline-induced contractions of the femoral arteries were elevated, while endothelium-dependent contractions were reduced in SHRu vs. SHRc. No differences were found in these parameters in WKY rats. In conclusion, the results indicated that the altered haemodynamics in SHR affect the tissue distribution and selected biological effects of FeO@PEG in the vasculature and liver, suggesting that caution should be taken when using iron oxide nanoparticles in hypertensive subjects.
我们研究了聚乙二醇（PEG）包覆的磁铁矿（FeO@PEG）纳米颗粒（核心尺寸约30 nm，流体动力学尺寸约51 nm，静脉注射，2 mg铁/千克/天，持续两天）在Wistar-Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）的主动脉和肝脏中的分布及生物学效应。FeO@PEG对旷场行为没有影响，但与FeO@PEG处理的WKY大鼠（WKYu）和生理盐水处理的对照SHR大鼠（SHRc）相比，显著降低了FeO@PEG处理的SHR大鼠（SHRu）的血压（BP）。与WKYu相比，SHRu的主动脉和肝脏中FeO@PEG含量显著升高。一氧化氮合酶（NOS）活性在主动脉中未改变，但与SHRc相比，SHRu肝脏中的NOS活性显著增加。在主动脉中，FeO@PEG处理增加了 和 基因表达（视为主要效应）。在肝脏中，与SHRc相比，FeO@PEG显著提高了SHRu中 和 基因表达，以及 和 基因表达（视为主要效应）。与SHRc相比，SHRu中去甲肾上腺素诱导的股动脉收缩增强，而内皮依赖性收缩减弱。WKY大鼠在这些参数上没有差异。总之，结果表明SHR中改变的血流动力学影响了FeO@PEG在血管系统和肝脏中的组织分布及特定生物学效应，这表明在高血压患者中使用氧化铁纳米颗粒时应谨慎。
