In this study, the effects of zinc oxide nanoparticle (ZnO-NP) exposure on the endothelial barrier and the pathway of ZnO-NPs to cross the endothelial barrier were examined. C57 mice were exposed to ZnO-NPs (1.2 mg/kg and 6 mg/kg body weight) and ZnSO₄ (3.6 mg/kg). Zinc biodistribution and toxicity tests, including H&E staining, TUNEL and 8-OHdG IHC staining of highly vascularized organs (liver, kidney and spleen), were assessed. Endothelial barrier disruption was assessed by interendothelial junction IHC staining of the thoracic aorta, and was further studied in human umbilical vein endothelial cells (HUVECs). Four different kinds of endocytosis inhibitors were also used to study the endocytosis effects of the ZnO-NPs on the HUVECs. We found that a significantly increased concentration of zinc was detected in the highly vascularized organs from the ZnO-NP exposure groups, together with histopathologic changes such as higher apoptotic death and oxidative status. Interendothelial junction disruption and increased endothelial barrier permeability were found in both the in vivo and in vitro experiments. All four endocytosis inhibitors were able to reduce the uptake and transport of ZnO-NPs in the HUVECs. We concluded that ZnO-NPs may impair endothelial cells and induce endothelial barrier dysfunction and are able to cross the endothelial barrier through paracellular and transcellular routes.

中文翻译：

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氧化锌纳米粒子体内和体外诱导的内皮屏障功能障碍及其穿越内皮屏障的机制。

在这项研究中，研究了氧化锌纳米颗粒（ZnO-NP）暴露对内皮屏障的影响以及ZnO-NPs穿越内皮屏障的途径。使C57小鼠暴露于ZnO-NPs（1.2mg / kg和6mg / kg体重）和ZnSO 4（3.6mg / kg）。评估了锌的生物分布和毒性测试，包括高度血管化器官（肝脏，肾脏和脾脏）的H＆E染色，TUNEL和8-OHdG IHC染色。内皮屏障的破坏通过胸主动脉的内皮间连接IHC染色进行评估，并在人脐静脉内皮细胞（HUVEC）中进行了进一步研究。还使用四种不同的内吞抑制剂来研究ZnO-NP对HUVEC的内吞作用。我们发现在ZnO-NP暴露组中高度血管化的器官中检测到锌的浓度显着增加，同时还发现组织病理学变化，例如更高的细胞凋亡死亡和氧化状态。两者均发现内皮间连接破坏和内皮屏障通透性增加。体内和体外实验。所有四种内吞抑制剂均能够减少HUVEC中ZnO-NP的摄取和转运。我们得出的结论是，ZnO-NPs可能损害内皮细胞并诱导内皮屏障功能障碍，并能够通过细胞旁和跨细胞途径穿越内皮屏障。