生物体内硒化氢气体递送及检测研究进展

doi:10.6023/A25110365

化学学报 ›› 2026, Vol. 84 ›› Issue (3): 448-458.DOI: 10.6023/A25110365 上一篇

综述

生物体内硒化氢气体递送及检测研究进展

莫秋红, 张峻, 尚品, 周怡波^*(), 卿志和

长沙理工大学化学与医药工程学院长沙 410000

投稿日期:2025-11-11 发布日期:2025-12-16
通讯作者: 周怡波

作者简介:

莫秋红, 2023年长沙理工大学在读硕士研究生, 主要从事有机小分子探针合成及其在生物化学传感与生物成像领域的应用.

张峻, 2025年长沙理工大学在读博士研究生, 主要从事聚合物信号放大探针的构建及其在生物化学传感与生物成像领域的应用.

尚品, 2024年长沙理工大学在读硕士研究生, 主要从事有机小分子荧光探针的构建及其在生物化学传感与生物成像领域的应用.

周怡波, 副教授, 硕士生导师, 长沙市杰青, 湖南省青年骨干教师. 2017年获湖南大学化学博士学位; 2018年至今工作于长沙理工大学, 2025年至英国巴斯大学化学系访问学者. 在Angew. Chem. Int. Ed.、Anal. Chem.、Biosens. Bioelectron等期刊发表论文30余篇. 获得湖南省自然科学二等奖、湖南省化学化工学会第十八届青年化学化工奖、湖南省优秀硕士学位论文指导教师等荣誉.

卿志和, 教授, 博士生导师, “国家优秀青年科学基金”获得者. 2014年获湖南大学化学博士学位; 2015年至今工作于长沙理工大学, 其间, 2019年至2020年于(加拿大)滑铁卢大学化学系访问学者. 从事化学生物传感与荧光成像研究, 相关成果发表在 PNAS、Angew. Chem.、Chem. Sci.、Anal. Chem.、 CCS Chem.等国内外高水平期刊上, 授权国家发明专利10余项. 担任Chin. Chem. Lett.、The Innovation、《分析试验室》等国内外期刊的编委或青年编委. 获得湖南省自然科学一等奖、湖南省青年科技奖、湖南省优秀研究生导师等.

基金资助:
项目受国家自然科学基金(22222402); 项目受国家自然科学基金(22474012); 湖南省自然科学基金(2024JJ3001); 湖南省自然科学基金(2025JJ50061); 长沙市杰出青年科学基金(kq2506009)

Research Progress on Delivery and Detection of Hydrogen Selenide in Vivo

Mo Qiuhong, Zhang Jun, Shang Pin, Zhou Yibo^*(), Qing Zhihe

School of Chemistry and Pharmaceutical Engineering, Changsha University of Science & Technology, Changsha 410000

Received:2025-11-11 Published:2025-12-16
Contact: Zhou Yibo
Supported by:
National Natural Science Foundation of China(22222402); National Natural Science Foundation of China(22474012); Natural Science Foundation of Hunan Province(2024JJ3001); Natural Science Foundation of Hunan Province(2025JJ50061); Scientific and Technological Plan Project of Changsha of China(kq2506009)

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摘要/Abstract

硒化氢(H₂Se)作为继NO、CO、H₂S后第四种被证实具有重要信号转导功能的内源性气体递质, 在生物体内具有多种重要的生理功能, 包括抗氧化、细胞信号传导和基因表达调控等. 然而, 由于其高毒性和不稳定性, 硒化氢的检测、供体合成及其在生物医学中的应用研究仍面临诸多挑战. 针对此问题, 已有文章报道多种基于水解反应或亲核反应的硒化氢供体, 同时利用硒化氢特异性反应设计合成多种不同识别位点的荧光探针, 通过细胞成像证明硒化氢供体能够显著增强细胞的抗氧化能力, 抑制炎症反应, 并在多种细胞模型中展现出良好的生物活性. 本综述主要针对硒化氢供体合成、释放机制、硒化氢的检测以及其在生物医学中的潜在应用等领域进行了归纳总结, 并对该领域的发展前景进行了展望.

关键词: 硒化氢, 分子供体, 生物传感, 细胞成像

Hydrogen selenide (H₂Se), recognized as the fourth endogenous gaseous neurotransmitter after NO, CO, and H₂S, plays a significant role in signal transduction. It is involved in various essential physiological processes, including antioxidant defense, cellular signal transduction, and regulation of gene expression. Additionally, H₂Se is vital for maintaining cellular redox balance and protecting cells from oxidative stress damage. Studies have shown that selenium is an essential trace element for the human body, and H₂Se is a key active substance produced during selenium metabolism. Its biological functions were similar as other gaseous signaling molecules, such as hydrogen sulfide, but it also exhibits unique chemical properties. However, the direct detection of H₂Se is challenging because of the high toxicity, extremely low stability, and rapid decomposition in aqueous solutions. To address these challenges, researchers are focused on developing donor molecules that remain stable under physiological conditions and release H₂Se via stimulation. In recent years, several novel H₂Se donors based on hydrolysis or nucleophilic substitution reactions have been reported. These compounds can gradually release H₂Se under specific conditions, thereby safely regulating its biological effects. Meanwhile, to monitor the dynamic fluctuation of H₂Se in living cells, a variety of highly selective and sensitive fluorescent probes have been developed, which were activated through specific chemical reactions at the recognition site. Experimental results have shown that the exogenous H₂Se donors rapidly distribute into the cytoplasm after entering the cells and significantly enhance the activity of intracellular antioxidant enzymes, such as glutathione peroxidase. Also, the H₂Se not only effectively eliminates excessive reactive oxygen species (ROS) and alleviates the cell damage caused by oxidative stress, but also exerts anti-inflammatory effects. This review primarily summarizes topics such as the synthesis and release mechanisms of H₂Se donors, detection of H₂Se, aiming to explore the future development prospects in the field of H₂Se.

Key words: hydrogen selenide, donor, biosensing, cell imaging

引用此文

莫秋红, 张峻, 尚品, 周怡波, 卿志和. 生物体内硒化氢气体递送及检测研究进展[J]. 化学学报, 2026, 84(3): 448-458.

Mo Qiuhong, Zhang Jun, Shang Pin, Zhou Yibo, Qing Zhihe. Research Progress on Delivery and Detection of Hydrogen Selenide in Vivo[J]. Acta Chimica Sinica, 2026, 84(3): 448-458.

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图/表 10

图式1. 硒化氢的递送与生物传感示意图

Scheme 1. Schematic of hydrogen selenide delivery and biosensing

图1. (a) TDN1042的合成; (b) TDN1042的水解过程[44]; (c) TDN1042与(d) 2AP-PSe的反应示意图; (e)与2AP-PSe共同孵育的HeLa细胞的飞行时间二次离子质谱图像[45]

Figure 1. (a) Synthesis of TDN1042; (b) Hydrolysis process of TDN1042[44] (Copyright 2019 Royal Society of Chemistry). Schematic of the reaction between (c) TDN1042 and (d) 2AP-PSe; (e) TOF-SIMS images of HeLa cells co-incubated with 2AP-PSe[45] (Copyright 2021 American Chemical Society)

图2. (a)半胱氨酸激活的H2Se供体释放示意图; (b)硒酰胺的动力学机制示意图[46]; (c)触发式H₂Se供体通用平台示意图及其在荧光供体中的应用; (d) H₂Se供体合成路径示意图与H2Se释放机制[47]; (e)可触发的H2Se供体和分析物替换型荧光探针示意图[48]

Figure 2. (a) Schematic of cysteine-activated donor release of H2Se; (b) Schematic of the kinetic mechanism of Selenamide[46] (Copyright 2022 American Chemical Society). (c) Schematic of triggered H2Se donor universal platform and Its application in fluorescent donor; (d) Schematic of H2Se donor synthesis pathway and H2Se release mechanism[47] (Copyright 2024 American Chemical Society); (e) General FITA platform for developing H2Se-activated donors and analyte-replacement fluorescent probe[48] (Copyright 2025 American Chemical Society)

图3. (a) IN-D的合成与响应机制; (b) DCI-H2Se的合成路线与识别机制; (c) DCI-H2Se对H2Se的荧光特性[49]

图4. (a) H2Se供体合成路径; (b) H2Se释放机制; (c) H2Se检测机制示意图[50]; (d) γ-酮硒醚的合成; (e) H2Se供体的释放机制示意图; (f)不同H2Se供体释放速率的比较[51]

Figure 4. (a) Synthesis of H2Se donor; (b) The release mechanism of H2Se; (c) Schematic of the detection mechanism of H2Se[50] (Copyright 2024 Royal Society of Chemistry); (d) Synthesis of γ-ketoselenylether; (e) Schematic of the release mechanism of H2Se donors; (f) Comparison of various kinds of H2Se donors with different release rates[51] (Copyright 2024 Royal Society of Chemistry)

图5. 常氧和低氧下亚硒酸盐诱导H2Se释放机制[52]

图6. H2Se-NG释放H2Se用于重耐药细菌感染治疗机制[53]

图7. (a) Se-Hyd与Se-Acid的合成路线及H2Se释放机制; (b)小鼠体内H2Se参与信号通路示意图[54]

Figure 7. (a) Synthetic routes of Se-Hyd and Se-Acid and the release mechanism of H2Se; (b) Schematic diagram of the H2Se involved in signaling pathways in mice[54] (Copyright 2024 The Innovation Life)

图8. (a) NIR-H2Se的合成与响应机制; (b) NIR-H2Se对H2Se的选择性及实时荧光响应H2Se[69]; (c)介孔硅纳米探针NIR-H2Se用于检测H2Se[75]; (d) Se-1探针对H2Se的响应机制; (e)常氧与缺氧条件下活细胞的荧光共聚焦图像[74]

Figure 8. (a) Synthesis and response mechanism of NIR-H2Se; (b) Selectivity and real time fluorescent response of NIR-H2Se to H2Se[69] (Copyright 2015 Royal Society of Chemistry); (c) The mesoporous silicon nanoprobe NIR-H2Se is used for the detection of H2Se[75] (Copyright 2018 American Chemical Society). (d) Response mechanism of Se-1 probe to H2Se; (e) Fluorescence confocal images of living cells under normoxic and hypoxic conditions[74] (Copyright 2015 Royal Society of Chemistry)

图9. (a) Hcy-H2Se对H2Se的响应机制; (b)常氧与缺氧条件下Hcy-H2Se处理的活细胞荧光共聚焦图像[70]. (c) HBT-Se的检测机制; (d)基于纸基的HBT-Se传感机制[71]

Figure 9. (a) Response mechanism of Hcy-H2Se toward H2Se; (b) Fluorescence confocal images of living cells incubated with Hcy-H2Se under normoxic and hypoxic conditions[70] (Copyright 2017 American Chemical Society). (c) Detection mechanism of HBT-Se; (d) Schematic diagram of HBT-Se paper-based sensor[71] (Copyright 2020 Elsevier)

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生物体内硒化氢气体递送及检测研究进展

Research Progress on Delivery and Detection of Hydrogen Selenide in Vivo

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