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构建用于检测2型糖尿病和非酒精性脂肪性肝炎中粘度变化的线粒体靶向近红外荧光探针。

Construction of a mitochondrial-targeting near-infrared fluorescent probe for detection of viscosity changes in type 2 diabetes mellitus and nonalcoholic steatohepatitis.

作者信息

Ren Xiaowen, Sayed Zahid Nasim, Shi Suntao, Hao Junlei, Gao Jia, Wu Jiang, Zhang Haijuan, Liu Zitong, Zhang Baoxin

机构信息

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.

State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China; Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province, College of Pharmacy, Qinghai Minzu University, Xining, 810007, Qinghai, China.

出版信息

Talanta. 2025 May 1;286:127470. doi: 10.1016/j.talanta.2024.127470. Epub 2024 Dec 26.

Abstract

The intracellular viscosity plays a pivotal role as a physicochemical factor and an important indicator of organelles performance. Abnormal changes in subcellular viscosity are often associated with cellular malfunction and various diseases. Nonalcoholic steatohepatitis (NASH) is the most common liver disease related with type 2 diabetes mellitus (T2DM), and both are linked to aberrant mitochondrial viscosity. In this study, we styled and screened a novel near-infrared probe termed MT-E, carrying the double bonds as the viscosity response groups, that was employed to image the viscosity changes in HepG2 cells, zebrafish and animal models. MT-E has a superior mitochondrial targeting ability, as well as a large Stokes shift (167 nm). Additionally, utilizing the excellent performance of MT-E, we first monitored the increased viscosity trends in both T2DM mice and NASH mice, suggesting that there is a strong correlation between T2DM and NASH. More groundbreakingly, we have successfully revealed, from fluorescence imaging, the extraordinary potential of Aloin in treating T2DM mice that can effectively reduce viscosity. This is a sign that MT-E may have a steering role in mitochondrial viscosity-associated disorders.

摘要

细胞内粘度作为一种物理化学因素和细胞器性能的重要指标,发挥着关键作用。亚细胞粘度的异常变化通常与细胞功能障碍和各种疾病相关。非酒精性脂肪性肝炎(NASH)是与2型糖尿病(T2DM)相关的最常见肝脏疾病,两者都与线粒体粘度异常有关。在本研究中,我们设计并筛选了一种新型近红外探针MT-E,它带有双键作为粘度响应基团,用于成像HepG2细胞、斑马鱼和动物模型中的粘度变化。MT-E具有优异的线粒体靶向能力,以及较大的斯托克斯位移(167 nm)。此外,利用MT-E的优异性能,我们首次监测了T2DM小鼠和NASH小鼠中粘度增加的趋势,表明T2DM和NASH之间存在很强的相关性。更具开创性的是,我们通过荧光成像成功揭示了芦荟素在治疗T2DM小鼠方面的非凡潜力,它可以有效降低粘度。这表明MT-E可能在线粒体粘度相关疾病中发挥指导作用。

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