基于碳氮双键构建粘度响应探针：“高保真”监测急性肝损伤研究
Construction of Viscosity-Responsive Probes Based on Carbon-Nitrogen Double Bonds: A Study on “High-Fidelity” Monitoring of Acute Liver Injury
摘要: 近年来，药物滥用、病毒感染及过度饮酒等致病因素的叠加，导致急性肝损伤的发病率持续攀升。当前临床诊断主要依赖血清生化指标检测和影像学评估，但这些手段在早期阶段常因灵敏度不足、特异性有限而导致漏诊，致使患者错过最佳干预时机。发展兼具时效性与精准度的早期诊断技术，已成为临床肝病诊疗领域亟待突破的核心问题。本研究成功开发了一种基于碳氮双键(C=N)旋转机制的新型近红外(NIR)荧光探针，用于超灵敏响应微环境粘度变化。该探针展现出优异的选择性、超高灵敏度、出色的光稳定性及宽pH耐受性等特性。结果表明，它能有效监测由脂多糖(LPS)诱导的炎症模型中细胞粘度的升高，并成功应用于对乙酰氨基酚(APAP)诱导的肝损伤模型中细胞内粘度的实时成像监测。该探针为研究细胞粘度相关的生理病理过程，特别是为急性肝损伤的早期监测提供了有力手段。
Abstract: In recent years, the incidence rate of acute liver injury has been continuously rising due to the combination of pathogenic factors such as drug abuse, viral infection, and excessive alcohol consumption. Current clinical diagnosis mainly relies on serum biochemical indicator testing and imaging assessments, but these methods often lead to missed diagnoses in the early stages due to insufficient sensitivity and limited specificity, resulting in patients missing the optimal intervention window. Developing early diagnostic techniques that are both timely and precise has become a core issue urgently requiring breakthroughs in the field of clinical liver disease diagnosis and treatment. This study successfully developed a novel near-infrared (NIR) fluorescent probe based on the rotation mechanism of carbon-nitrogen double bonds (C=N) for ultra-sensitive response to changes in microenvironment viscosity. The probe exhibits excellent selectivity, ultra-high sensitivity, outstanding photostability, and wide pH tolerance. The results demonstrate that it can effectively monitor the increase in cell viscosity in an inflammation model induced by lipopolysaccharide (LPS) and has been successfully applied to real-time imaging monitoring of intracellular viscosity in a liver injury model induced by acetaminophen (APAP). This probe provides a powerful tool for studying physiological and pathological processes related to cell viscosity, especially for the early monitoring of acute liver injury.
文章引用：王盛, 颜健奇, 倪朝舜, 甘亚兵, 聂立波. 基于碳氮双键构建粘度响应探针：“高保真”监测急性肝损伤研究[J]. 生物医学, 2026, 16(3): 359-368. https://doi.org/10.12677/hjbm.2026.163038

参考文献

[1] Robinson, M.W., Harmon, C. and O’Farrelly, C. (2016) Liver Immunology and Its Role in Inflammation and Homeostasis. Cellular & Molecular Immunology, 13, 267-276. [Google Scholar] [CrossRef] [PubMed]
[2] Sun, J., Cao, L., Dong, M., Liu, Y., Wang, Y. and Zhan, Y. (2026) HOCL and Viscosity Dual-Responsive Fluorescent Probe for Accurate Discrimination between Early Hepatocellular Carcinoma and Acute Liver Injury. Materials Today Bio, 37, Article 102816. [Google Scholar] [CrossRef] 
[3] Tak, J., Kim, Y.S. and Kim, S.G. (2025) Roles of X-Box Binding Protein 1 in Liver Pathogenesis. Clinical and Molecular Hepatology, 31, 1-31. [Google Scholar] [CrossRef] [PubMed]
[4] 尹一峰, 胡启辉, 杜毅超, 等. 细胞外基质在肝细胞性肝癌发生发展过程中的作用[J]. 中国普通外科杂志, 30(1): 91-97.
[5] 刘双庆, 杨建中, 杨婷, 等. 成人急性肝损伤诊疗急诊专家共识[J]. 中国急救医学, 2024, 44(1): 5-12.
[6] Paul, B.W. and Merrie, M. (2018) Mechanisms of Drug-Induced Liver Injury. In: Schiff, E.R., Maddrey, W.C. and Reddy, K.R., Eds., Schiff’s Diseases of the Liver, Twelfth Edition, John Wiley & Sons Ltd., 774-798.
[7] Xu, J.J., Diaz, D. and O’Brien, P.J. (2004) Applications of Cytotoxicity Assays and Pre-Lethal Mechanistic Assays for Assessment of Human Hepatotoxicity Potential. Chemico-Biological Interactions, 150, 115-128. [Google Scholar] [CrossRef] [PubMed]
[8] Pugh, A.J., Barve, A.J., Falkner, K., Patel, M. and McClain, C.J. (2009) Drug-Induced Hepatotoxicity or Drug-Induced Liver Injury. Clinics in Liver Disease, 13, 277-294. [Google Scholar] [CrossRef] [PubMed]
[9] Qin, J., Kong, F., Huang, J., Xiao, B., Bian, Y. and Shao, C. (2025) Lysosome-Targeted Dual-Locked NIR Fluorescent Probe for Visualization of H2S and Viscosity in Drug-Induced Liver Injury and Tumor Models. Analytica Chimica Acta, 1337, Article 343558. [Google Scholar] [CrossRef] [PubMed]
[10] Zhang, X., Wu, W., Wei, Y., Zhang, Y., Nie, X., Sun, X., et al. (2024) A Fret-Based Multifunctional Fluorescence Probe for the Simultaneous Detection of Sulfite and Viscosity in Living Cells. Bioorganic Chemistry, 148, Article 107423. [Google Scholar] [CrossRef] [PubMed]
[11] Sun, X., Wang, J., Shang, Z., Wang, H., Wang, Y. and Shuang, S. (2024) A Triphenylamine-Thiophene-Based Fluorescent Probe for the Dual-Channel Detection and Imaging of Hypochlorite and Viscosity in Live Cells. Journal of Molecular Liquids, 402, Article 124788. [Google Scholar] [CrossRef] 
[12] Yin, J., Huang, L., Wu, L., Li, J., James, T.D. and Lin, W. (2021) Small Molecule Based Fluorescent Chemosensors for Imaging the Microenvironment within Specific Cellular Regions. Chemical Society Reviews, 50, 12098-12150. [Google Scholar] [CrossRef] [PubMed]
[13] Robson, J.A., Kubánková, M., Bond, T., Hendley, R.A., White, A.J.P., Kuimova, M.K., et al. (2020) Simultaneous Detection of Carbon Monoxide and Viscosity Changes in Cells. Angewandte Chemie, 132, 21615-21619. [Google Scholar] [CrossRef] 
[14] Wolstenholme, C.H., Hu, H., Ye, S., Funk, B.E., Jain, D., Hsiung, C., et al. (2020) AggFluor: Fluorogenic Toolbox Enables Direct Visualization of the Multi-Step Protein Aggregation Process in Live Cells. Journal of the American Chemical Society, 142, 17515-17523. [Google Scholar] [CrossRef] [PubMed]
[15] Cheng, D., Xu, W., Gong, X., Yuan, L. and Zhang, X. (2021) Design Strategy of Fluorescent Probes for Live Drug-Induced Acute Liver Injury Imaging. Accounts of Chemical Research, 54, 403-415. [Google Scholar] [CrossRef] [PubMed]
[16] Chao, J., Liao, Q., Hu, L., Wang, Z., Peng, Z., Mao, G., et al. (2024) Near-infrared Fluorescent Probe for the Imaging of Viscosity in Fatty Liver Mice and Valuation of Drug Efficacy. Talanta, 276, Article 126227. [Google Scholar] [CrossRef] [PubMed]
[17] Fu, M., He, F., Jiang, Z., Chen, X., Xie, Z. and Hu, J. (2023) Development of a Novel Near-Infrared Molecule Rotator for Early Diagnosis and Visualization of Viscosity Changes in Acute Liver Injury Models. RSC Advances, 13, 26247-26251. [Google Scholar] [CrossRef] [PubMed]
[18] 雷玮, 王丹丹, 葛广波, 等. 肝损伤血清标志物研究进展[J]. 实用肝脏病杂志, 2017, 20(2): 252-256.
[19] Dai, B., Jiang, S., Wang, W., Li, Z. and Feng, G. (2025) Decreased Lysosomal Polarity during Acute Alcoholic Liver Injury Revealed by a Near-Infrared Fluorescent Probe. Analytical Chemistry, 97, 17102-17110. [Google Scholar] [CrossRef] [PubMed]
[20] Zhang, Y., Jiang, Q., Wang, K., Fang, Y., Zhang, P., Wei, L., et al. (2024) Dissecting Lysosomal Viscosity Fluctuations in Live Cells and Liver Tissues with an Ingenious NIR Fluorescent Probe. Talanta, 272, Article 125825. [Google Scholar] [CrossRef] [PubMed]
[21] Yang, H., Chen, Y., He, J., Li, Y. and Feng, Y. (2025) Advances in the Diagnosis of Early Biomarkers for Acute Kidney Injury: A Literature Review. BMC Nephrology, 26, Article No. 115. [Google Scholar] [CrossRef] [PubMed]
[22] Li, N., Liu, Z., Chen, C., Jiang, H., Liu, Y. and Ni, D. (2025) Activatable Fluorescent Ratiometric Probes for Early Diagnosis and Prognostic Assessment of Acute Kidney Injury. Science Advances, 11, eaea1654. [Google Scholar] [CrossRef] 
[23] Wu, Q., Zhou, Q., Li, W., Ren, T., Zhang, X. and Yuan, L. (2022) Evolving an Ultra-Sensitive Near-Infrared β-Galactosidase Fluorescent Probe for Breast Cancer Imaging and Surgical Resection Navigation. ACS Sensors, 7, 3829-3837. [Google Scholar] [CrossRef] [PubMed]
[24] Lei, P., Wang, R., Dong, C., Shuang, S. and Li, M. (2024) Mitochondria-Targeted NIR Molecular Probe for Detecting Viscosity of Gland Damage and SO2 in Actual Samples. Journal of Industrial and Engineering Chemistry, 140, 658-664. [Google Scholar] [CrossRef] 
[25] Xu, S., Liu, H., Yin, X., Yuan, L., Huan, S. and Zhang, X. (2019) A Cell Membrane-Anchored Fluorescent Probe for Monitoring Carbon Monoxide Release from Living Cells. Chemical Science, 10, 320-325. [Google Scholar] [CrossRef] [PubMed]
[26] Zhang, J., Zhu, X., Hu, X., Liu, H., Li, J., Feng, L., et al. (2016) Ratiometric Two-Photon Fluorescent Probe for in Vivo Hydrogen Polysulfides Detection and Imaging during Lipopolysaccharide-Induced Acute Organs Injury. Analytical Chemistry, 88, 11892-11899. [Google Scholar] [CrossRef] [PubMed]
[27] Huang, J. and Pu, K. (2021) Near-Infrared Fluorescent Molecular Probes for Imaging and Diagnosis of Nephro-Urological Diseases. Chemical Science, 12, 3379-3392. [Google Scholar] [CrossRef] [PubMed]
[28] Yang, M., Huang, J., Fan, J., Du, J., Pu, K. and Peng, X. (2020) Chemiluminescence for Bioimaging and Therapeutics: Recent Advances and Challenges. Chemical Society Reviews, 49, 6800-6815. [Google Scholar] [CrossRef] [PubMed]
[29] Feng, Y., Nie, G., Liang, W., Li, W., Zhang, Y., Wang, K., et al. (2022) Real-Time Imaging of Acute Alcoholic Liver Injury in Vivo via a Robust Viscosity Probe with Aggregation-Induced Emission Nature. Sensors and Actuators B: Chemical, 355, Article 131285. [Google Scholar] [CrossRef] 
[30] Yin, J., Xu, L., Yang, H., Qi, W., Ren, X., Zheng, X., et al. (2023) Construction of a Label-Detection Integrated Visual Probe to Reveal the Double-Edged Sword Principle of Ferroptosis in Liver Injury. Analytical Chemistry, 96, 355-363. [Google Scholar] [CrossRef] [PubMed]
[31] Dou, K., Huang, W., Xiang, Y., Li, S. and Liu, Z. (2020) Design of Activatable NIR-II Molecular Probe for in Vivo Elucidation of Disease-Related Viscosity Variations. Analytical Chemistry, 92, 4177-4181. [Google Scholar] [CrossRef] [PubMed]
[32] Peng, C., Ma, X., Lin, D., Feng, X., Yu, H. and Li, Y. (2021) A Novel Near-Infrared Viscosity Probe Based on Synergistic Effect of AIE Property and Molecular Rotors for Mitophagy Imaging during Liver Injury. Analytica Chimica Acta, 1187, Article 339146. [Google Scholar] [CrossRef] [PubMed]
[33] Zhou, Y., Liu, Z., Qiao, G., Tang, B. and Li, P. (2021) Visualization of Endoplasmic Reticulum Viscosity in the Liver of Mice with Nonalcoholic Fatty Liver Disease by a Near-Infrared Fluorescence Probe. Chinese Chemical Letters, 32, 3641-3645. [Google Scholar] [CrossRef] 
[34] Tang, Y., Peng, J., Zhang, Q., Song, S. and Lin, W. (2022) A New NIR Emission Mitochondrial Targetable Fluorescent Probe and Its Application in Detecting Viscosity Changes in Mouse Liver and Kidney Injury. Talanta, 249, Article 123647. [Google Scholar] [CrossRef] [PubMed]
[35] Peng, H., Jing, X., Han, S. and Lin, W. (2024) Detecting Viscosity Changes in the Limb Ischemia-Reperfusion in Mice with a Near-Infrared Fluorescence Probe. Analytica Chimica Acta, 1311, Article 342733. [Google Scholar] [CrossRef] [PubMed]
[36] Wang, X., Yin, Z., Liu, H., Wang, Z., Zhu, X. and Ye, Y. (2024) A Novel NIR Fluorescence Probe with AIE Property to Image Viscosity in Nystatin-Induced Cell Model. Journal of Fluorescence, 35, 2935-2942. [Google Scholar] [CrossRef] [PubMed]
[37] Liao, Q., Chao, J., Wang, W., Liu, T., Mao, G., Xu, F., et al. (2023) A Novel Near-Infrared Fluorescent Probe for the Imaging of Viscosity in Cells and Tumor-Bearing Mice. Chemical Communications, 59, 5607-5610. [Google Scholar] [CrossRef] [PubMed]
[38] Zhang, X., He, X., Si, Y., Nie, X., Lun, S., Wang, C., et al. (2025) A Dual Sensitive Fluorescence Probe for the Simultaneous Visualization of Hypochlorite and Viscosity in Living Cells and Zebrafish. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 325, Article 125149. [Google Scholar] [CrossRef] [PubMed]

为你推荐