Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, PR China.
College of Chemical Engineering, Xiangtan University, Xiangtan, 411105, P.R. China.
Anal Chem. 2020 Mar 17;92(6):4244-4250. doi: 10.1021/acs.analchem.9b04578. Epub 2020 Mar 3.
Liver fibrosis is a major stage in the development of liver disease, and it is important to investigate its pathogenesis for early intervention or even reversal. Recent studies have found that intestinal disease can aggravate liver fibrosis through the role of the "gut-liver axis". Hypoxia is considered to be a typical characteristic of many diseases including ulcerative colitis and liver fibrosis. However, there is no fluorescent probe for hypoxia detection to investigate the "gut-liver axis". Herein we design and synthesize a turn-on fluorescent probe termed Cy-AP, which displays high sensitivity and selectivity to hypoxia given by sodium dithionite (NaSO) in vitro with near-infrared (NIR) emission (725 nm). The possible response mechanism of Cy-AP toward hypoxia is given and proved though HPLC, MS, and theory calculation. Moreover, on the basis of low cell cytotoxicity, the probe is used in visualizing hypoxia in four cell lines (HepG2, HCT116, HeLa, and MCF-7 cells) by fluorescence imaging, flow cytometry, and 3D imaging. Furthermore, due to its NIR emission, Cy-AP can monitor the hypoxia condition in vivo such as in liver fibrosis mice and ulcerative colitis mice models. In particular, the probe can validate the existence and mechanism of the "gut-liver axis" in vivo by monitoring hypoxia. To the best of our knowledge, this is the first work to give a strategy for studying the "gut-liver axis" by a NIR hypoxia-sensitive fluorescent probe, which will provide some powerful support for delaying the progression of liver fibrosis and thus promoting the treatment of liver disease.
肝纤维化是肝病发展的主要阶段，研究其发病机制对于早期干预甚至逆转非常重要。最近的研究发现，肠道疾病可以通过“肠-肝轴”的作用加重肝纤维化。缺氧被认为是溃疡性结肠炎和肝纤维化等许多疾病的典型特征。然而，目前还没有用于检测“肠-肝轴”的缺氧荧光探针。在此，我们设计并合成了一种称为 Cy-AP 的开环型荧光探针，它在体外对连二亚硫酸钠（NaSO）表现出高灵敏度和选择性的近红外（NIR）发射（725nm）。通过 HPLC、MS 和理论计算，给出并证明了 Cy-AP 对缺氧的可能响应机制。此外，基于低细胞毒性，该探针可用于通过荧光成像、流式细胞术和 3D 成像可视化四种细胞系（HepG2、HCT116、HeLa 和 MCF-7 细胞）中的缺氧。此外，由于其近红外发射，Cy-AP 可以在体内监测缺氧情况，如肝纤维化小鼠和溃疡性结肠炎小鼠模型。特别是，该探针可以通过监测缺氧来验证“肠-肝轴”在体内的存在和机制。据我们所知，这是首次使用近红外敏感染料研究“肠-肝轴”的工作，这将为延缓肝纤维化的进展从而促进肝病的治疗提供有力支持。
