ROS响应性硫化氢供体-抗氧化酶复合纳米体系的构建及其治疗缺血再灌注肝损伤的研究
Construction of ROS-responsive hydrogen sulfide donor-antioxidant enzyme composite nanosystem and its application in the treatment of ischemia-reperfusion liver injury
摘要
针对肝缺血再灌注损伤中ROS暴发、炎症放大及细胞损伤等关键问题，设计并合成了ROS响应性硫化氢供体NHB，并构建了负载超氧化物歧化酶和过氧化氢酶的复合纳米体系NHB@SOD/CAT。该体系具有良好的粒径分布、稳定性及蛋白复合能力，可在高ROS环境下响应性降解并持续释放H2S。细胞实验显示，NHB@SOD/CAT具有良好生物相容性，能够显著提高缺氧/复氧损伤肝细胞存活率并降低胞内ROS水平。动物实验进一步证实，该体系可明显减轻肝组织坏死和病理损伤，改善氧化应激和炎症状态，并调控巨噬细胞向抗炎表型转化。研究表明，NHB@SOD/CAT通过H2S释放与抗氧化酶递送协同作用，可有效缓解肝缺血再灌注损伤，为HIRI防治提供了新的研究思路
Abstract
This study aimed to address the ROS burst, amplified inflammation, and cellular damage involved in hepatic ischemia-reperfusion injury (HIRI). A ROS-responsive hydrogen sulfide donor, NHB, was designed and synthesized, and a composite nanosystem, NHB@SOD/CAT, loaded with superoxide dismutase and catalase, was successfully constructed. The results showed that this nanosystem possessed favorable particle characteristics, stability, and protein-loading capacity, and could undergo ROS-responsive degradation with sustained H2S release under oxidative conditions. In vitro experiments demonstrated that NHB@SOD/CAT had good biocompatibility, significantly improved the viability of hepatocytes after hypoxia/reoxygenation injury, and effectively reduced intracellular ROS levels. In vivo studies further confirmed that the nanosystem markedly alleviated hepatic necrosis and histopathological damage, improved oxidative stress and inflammatory responses, and promoted macrophage polarization toward an anti-inflammatory phenotype. Overall, NHB@SOD/CAT effectively attenuated HIRI through the synergistic effects of controlled H2S release and antioxidant enzyme delivery, providing a promising strategy for HIRI treatment.关键词
肝缺血再灌注损伤/硫化氢供体/抗氧化酶/ROS响应/协同治疗Key words
hepatic ischemia-reperfusion injury/hydrogen sulfide donor/antioxidant enzymes/ROS responsiveness/synergistic therapy引用本文复制引用
杨洁妤,冯旭利.ROS响应性硫化氢供体-抗氧化酶复合纳米体系的构建及其治疗缺血再灌注肝损伤的研究[EB/OL].(2026-04-23)[2026-04-24].http://www.paper.edu.cn/releasepaper/content/202604-178.学科分类
基础医学/临床医学/内科学
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