{"title":"化学发光探针通过焦谷氨酸氨基肽酶-1激活增强肾缺血再灌注损伤的可视化","authors":"Zhongkun Wang, Tingting Geng, Xiaoyi Yue, Zhixiong Zheng, Wei Zhang, Zhen Pan, Qunlin Zhang* and Xiang Shi*, ","doi":"10.1021/acs.analchem.4c0583810.1021/acs.analchem.4c05838","DOIUrl":null,"url":null,"abstract":"<p >The absence of an effective imaging tool for diagnosing renal ischemia-reperfusion injury (RIRI) severely delays its treatment, and currently, no definitive clinical interventions are available. Pyroglutamate aminopeptidase-1 (PGP-1), a potential inflammatory cytokine, has shown considerable potential as a biomarker for tracing the inflammatory process in vivo. However, its exact role in the enhanced visualization of RIRI in complex biological systems has yet to be fully established. Chemiluminescence imaging (CLI) has proven to be one of the most promising diagnostic methods due to its ultrahigh-contrast imaging capabilities compared to fluorescence imaging. In this study, we developed an activatable Schaap’s dioxetane chemiluminescent probe (PGP–PD) to explore the potential of PGP-1 as a marker for CLI of renal injury following ischemia-reperfusion, with the goal of achieving high-contrast in situ diagnostics for RIRI. In vitro, PGP–PD exhibited exceptional selectivity for exogenous PGP-1 and remarkable sensitivity, with a detection limit as low as 2.244 ng/mL. Moreover, in vivo studies successfully demonstrated a positive correlation between the RIRI and PGP-1 level. Notably, in situ imaging with PGP–PD generated a significant chemiluminescent signal within the RIRI-kidney, providing an exceptionally high contrast between injured and normal kidney tissue (∼9.4-fold) in the RIRI mouse model. We anticipate that this work may offer a valuable biomarker (PGP-1) and a powerful imaging tool for improving RIRI in situ diagnosis, thereby aiding treatment planning and surgical outcomes for RIRI patients.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":"97 4","pages":"2367–2374 2367–2374"},"PeriodicalIF":6.7000,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chemiluminescent Probe for Enhanced Visualization of Renal Ischemia-Reperfusion Injury via Pyroglutamate Aminopeptidase-1 Activation\",\"authors\":\"Zhongkun Wang, Tingting Geng, Xiaoyi Yue, Zhixiong Zheng, Wei Zhang, Zhen Pan, Qunlin Zhang* and Xiang Shi*, \",\"doi\":\"10.1021/acs.analchem.4c0583810.1021/acs.analchem.4c05838\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The absence of an effective imaging tool for diagnosing renal ischemia-reperfusion injury (RIRI) severely delays its treatment, and currently, no definitive clinical interventions are available. Pyroglutamate aminopeptidase-1 (PGP-1), a potential inflammatory cytokine, has shown considerable potential as a biomarker for tracing the inflammatory process in vivo. However, its exact role in the enhanced visualization of RIRI in complex biological systems has yet to be fully established. Chemiluminescence imaging (CLI) has proven to be one of the most promising diagnostic methods due to its ultrahigh-contrast imaging capabilities compared to fluorescence imaging. In this study, we developed an activatable Schaap’s dioxetane chemiluminescent probe (PGP–PD) to explore the potential of PGP-1 as a marker for CLI of renal injury following ischemia-reperfusion, with the goal of achieving high-contrast in situ diagnostics for RIRI. In vitro, PGP–PD exhibited exceptional selectivity for exogenous PGP-1 and remarkable sensitivity, with a detection limit as low as 2.244 ng/mL. Moreover, in vivo studies successfully demonstrated a positive correlation between the RIRI and PGP-1 level. Notably, in situ imaging with PGP–PD generated a significant chemiluminescent signal within the RIRI-kidney, providing an exceptionally high contrast between injured and normal kidney tissue (∼9.4-fold) in the RIRI mouse model. We anticipate that this work may offer a valuable biomarker (PGP-1) and a powerful imaging tool for improving RIRI in situ diagnosis, thereby aiding treatment planning and surgical outcomes for RIRI patients.</p>\",\"PeriodicalId\":27,\"journal\":{\"name\":\"Analytical Chemistry\",\"volume\":\"97 4\",\"pages\":\"2367–2374 2367–2374\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2025-01-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Analytical Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.analchem.4c05838\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ANALYTICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical Chemistry","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.analchem.4c05838","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
Chemiluminescent Probe for Enhanced Visualization of Renal Ischemia-Reperfusion Injury via Pyroglutamate Aminopeptidase-1 Activation
The absence of an effective imaging tool for diagnosing renal ischemia-reperfusion injury (RIRI) severely delays its treatment, and currently, no definitive clinical interventions are available. Pyroglutamate aminopeptidase-1 (PGP-1), a potential inflammatory cytokine, has shown considerable potential as a biomarker for tracing the inflammatory process in vivo. However, its exact role in the enhanced visualization of RIRI in complex biological systems has yet to be fully established. Chemiluminescence imaging (CLI) has proven to be one of the most promising diagnostic methods due to its ultrahigh-contrast imaging capabilities compared to fluorescence imaging. In this study, we developed an activatable Schaap’s dioxetane chemiluminescent probe (PGP–PD) to explore the potential of PGP-1 as a marker for CLI of renal injury following ischemia-reperfusion, with the goal of achieving high-contrast in situ diagnostics for RIRI. In vitro, PGP–PD exhibited exceptional selectivity for exogenous PGP-1 and remarkable sensitivity, with a detection limit as low as 2.244 ng/mL. Moreover, in vivo studies successfully demonstrated a positive correlation between the RIRI and PGP-1 level. Notably, in situ imaging with PGP–PD generated a significant chemiluminescent signal within the RIRI-kidney, providing an exceptionally high contrast between injured and normal kidney tissue (∼9.4-fold) in the RIRI mouse model. We anticipate that this work may offer a valuable biomarker (PGP-1) and a powerful imaging tool for improving RIRI in situ diagnosis, thereby aiding treatment planning and surgical outcomes for RIRI patients.
期刊介绍:
Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.