Application of biocompatible custom ceria nanoparticles in improving the quality of liver grafts for transplantation
Application of biocompatible custom ceria nanoparticles in improving the quality of liver grafts for transplantation
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DOI：
10.1007/s12274-022-5071-2
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发表时间：
2022-11
期刊：
影响因子：
9.9
通讯作者：
Yinbiao Qiao;Jian-Hui Li;Suchen Bian;Chenyue Zhan;Jia Luo;Li Jiang;Haoyu Li;Hao Wu;Cheng Zhang;Shusen Zheng;Haiyang Xie;P. Song
中科院分区：
文献类型：
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作者：
Yinbiao Qiao;Jian-Hui Li;Suchen Bian;Chenyue Zhan;Jia Luo;Li Jiang;Haoyu Li;Hao Wu;Cheng Zhang;Shusen Zheng;Haiyang Xie;P. Song
肝移植（Liver transplantation， LT）是治疗终末期肝病的一种终极和重要方法，常伴有供肝热缺血或冷缺血引起的缺血-再灌注损伤（ischemia-reperfusion injury， IRI）。器官保护技术用于提高肝移植的质量（从取出到植入）。活性氧（Reactive oxygen species， ROS）引起的氧化应激被认为是lt后IRI的关键因素。纳米抗氧化剂能够清除ROS，减轻多种器官和组织的IRI。在本研究中，我们采用热解法合成了具有抗氧化性能的氧化铈纳米颗粒（NPs），并在其表面覆盖磷脂-聚乙二醇，以提高其体内生物相容性。我们研究了氧化铈NPs潜在的器官保护作用及其机制。氧化铈NPs通过减轻肝移植术后IRI，促进肝移植术后肝功能恢复。采用体外低温氧合机器灌注法研究了氧化铈NPs对肝移植的保护作用。体外实验表明，氧化铈NPs通过增强线粒体活性和活性氧清除能力来减轻缺氧再氧化或h2o2诱导的肝细胞损伤。这些作用可能与核因子红细胞衍生2相关因子2 (Nrf2)/ kelch样ech相关蛋白1 (Keap1)/血红素加氧酶1 （HO-1）信号通路的激活有关。综上所述，氧化铈NPs可能是一种有前景的抗氧化剂，可用于肝移植后IRI的治疗。
Liver transplantation (LT), an ultimate and vital method for treating end-stage liver disease, is often accompanied by ischemia-reperfusion injury (IRI) resulting from warm or cold ischemia of the donor liver. Organ protection techniques are used to improve the quality of liver grafts (from retrieval to implantation). Reactive oxygen species (ROS) cause oxidative stress, which is considered a crucial factor in IRI after LT. Nano antioxidants capable of scavenging ROS alleviate IRI in multiple types of organs and tissues. In this study, we synthesized ceria nanoparticles (NPs) with antioxidant properties using a pyrolysis method and covered them with phospholipid-polyethylene glycol to improve their biocompatibilityin vivo. We investigated the potential organ-protective effect of ceria NPs and the underlying mechanisms. Ceria NPs promoted liver function recovery after LT by attenuating IRI in liver graftsin vivo. The protective effect of ceria NPs on liver grafts was investigated by applying hypothermic oxygenated machine perfusionex vivo. Ceria NPs attenuated hypoxia reoxygenation- or H2O2-induced hepatocyte injury by enhancing mitochondrial activity and ROS scavengingin vitro. These effects may be associated with the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)/heme oxygenase 1 (HO-1) signaling pathway. In conclusion, ceria NPs may serve as a promising antioxidant agent for the treatment of hepatic IRI after LT.