氧化铁纳米颗粒引起肝血窦内皮细胞损伤及其机制研究

doi:10.3969/j.issn.0258-8021.2021.05.09

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Abstract This work is aimed to investigate the effect of dimercaptosuccinic acid-magnetite nanoparticles (DMSA-Fe₃O₄) on hepatic sinusoid endothelial cells (HHSECs) in vitro and in vivo. Transmission electron microscopy and nanoparticle tracking analysis were applied to characterize the particle size and surface property. Real-time cellular analysis assay, flow cytometry, quantitative real-time PCR (q-PCR) and Prussian blue staining were applied to analyze the effect of DMSA-Fe₃O₄ to HHSECs with the concentration from 0 to 200 μg/mL. DMSA-Fe₃O₄ with the dose of 1 mg/kg was injected into mice through the tail vein to analyze liver damage. For cell experiments, n=3; For animal experiments, n=4. HHSECs engulfed DMSA-Fe₃O₄in a dose and time dependent manner, with cell viability decreasing to 37.3% of that for control group. DMSA-Fe₃O₄ engulfment increased the intracellular ROS of HHSECs to 1.41 folds. The expression of HO-1 of the cells was significantly increased to 20.8 folds of the control group, the expression of HIF-1α was increased to 2.01 folds of the control group,the expression of VEGF was increased to 4.2 folds of the control group. DMSA-Fe₃O₄were observed to accumulate in endothelial and Kupffer cells and induced liver damage on the 2nd day after the fourth injection. The amount of DMSA-Fe₃O₄ in the liver decreased significantly on day 158 and the hepatic damage was recovered. The DMSA-Fe₃O₄ nanoparticles was up-taken by HHSECs and induced cell oxidation related injury.In conclusion, multiple intravenous administrations of DMSA-Fe₃O₄ induced nanoparticle accumulation in the liver and its injury, which was recovered as DMSA-Fe₃O₄ being expelled from the liver over time.

Key words： iron oxide nanoparticles hepatic sinusoidal endothelial cells ROS liver engulfment

Received: 02 April 2021

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R318

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	Articles by authors
	Zhang Xue
	Kong Fei
	Wen Tao
	Zhang Yu
	Meng Jie
	Xu Haiyan

Cite this article:

Zhang Xue,Kong Fei,Wen Tao, et al. Iron Oxide Nanoparticles Induced Hepatic Sinusoid Endothelial Cells Damage and the Mechanism Research[J]. Chinese Journal of Biomedical Engineering, 2021, 40(5): 582-589.

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http://cjbme.csbme.org/EN/10.3969/j.issn.0258-8021.2021.05.09 OR http://cjbme.csbme.org/EN/Y2021/V40/I5/582

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