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利用新型探针对人胰腺脂肪酶活性进行荧光寿命成像,用于重症急性胰腺炎的早期诊断。

Fluorescence lifetime imaging of human pancreatic lipase activity using a novel probe for early diagnosis of severe acute pancreatitis.

机构信息

Affiliated Hospital of Nantong University, Nantong University, 226001 Nantong, China.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, No.163 Xianlin Road, Nanjing 210023, China.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2025 Feb 5;326:125171. doi: 10.1016/j.saa.2024.125171. Epub 2024 Sep 21.

Abstract

Severe Acute Pancreatitis, a serious condition caused by factors such as gallstones and chronic excessive alcohol consumption, with a very high mortality rate. Human pancreatic lipase (hPL) is a key digestive enzyme and abnormal activity levels of this enzyme are important indicators for diagnosing and monitoring pancreatic diseases. A fluorescent probe, LPP, has been developed to monitor the activity of hPL, especially in cases of SAP. The probe is based on cyanine isoindole derivatives, in vitro experiments confirmed the high specificity and sensitivity of the probe, with a detection limit of 0.012 U/mL, reactions completed within 10 min, and effective monitoring of pancreatic lipase activity in various biological samples. The stability and low cytotoxicity of LPP make it suitable for clinical applications, providing new tools and perspectives for the research and treatment of pancreatic diseases and related metabolic abnormalities. In addition, the change in fluorescence lifetime after the reaction of the probe with lipase allows for fluorescence lifetime imaging (FLIM), effectively monitoring the dynamic changes of hPL and enabling early diagnosis and monitoring of pancreatitis. This research not only enhances the understanding of pancreatic lipase activity detection but also has the potential to improve the diagnostics and treatment of pancreatitis.

摘要

重症急性胰腺炎是一种由胆结石和慢性过度饮酒等因素引起的严重疾病,死亡率非常高。人胰腺脂肪酶(hPL)是一种关键的消化酶,这种酶的异常活性水平是诊断和监测胰腺疾病的重要指标。已经开发出一种荧光探针 LPP 来监测 hPL 的活性,特别是在 SAP 的情况下。该探针基于氰基吲哚衍生物,体外实验证实了探针的高特异性和灵敏度,检测限为 0.012 U/mL,反应在 10 分钟内完成,并能有效监测各种生物样本中的胰腺脂肪酶活性。LPP 的稳定性和低细胞毒性使其适合临床应用,为胰腺疾病和相关代谢异常的研究和治疗提供了新的工具和视角。此外,探针与脂肪酶反应后的荧光寿命变化可实现荧光寿命成像(FLIM),有效监测 hPL 的动态变化,实现胰腺炎的早期诊断和监测。这项研究不仅增强了对胰腺脂肪酶活性检测的理解,还有望改善胰腺炎的诊断和治疗。

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