Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, PR China.
Hunan Provincial Key Laboratory of Water Treatment Functional Materials, College of Chemistry and Materials Engineering, Hunan University of Arts and Science, Changde 415000, PR China.
Anal Chem. 2024 Feb 27;96(8):3436-3444. doi: 10.1021/acs.analchem.3c04781. Epub 2024 Feb 19.
Cerebral ischemia-reperfusion injury (CIRI), a cause of cerebral dysfunction during cerebral infarction treatment, is closely associated with mitochondrial viscosity and hydrogen peroxide (HO). However, the accurate measurement of mitochondrial viscosity and HO levels in CIRI is challenging because of the lack of sufficient selectivity and blood-brain barrier (BBB) penetration of existing monitoring tools related to CIRI, hampering the exploration of the role of mitochondrial viscosity and HO in CIRI. To address this issue, we designed an activatable fluorescent probe, mitochondria-targeting styryl-quinolin-ium (), with excellent properties including high selectivity, mitochondrial targeting, and BBB penetration, for the visualization of mitochondrial viscosity and HO in the brain. Based on the real-time monitoring capabilities of the probe, bursts of mitochondrial viscosity and HO levels were visualized during CIRI. This probe can be used to monitor the therapeutic effects of butylphthalein treatment. More importantly, in vivo experiments further confirmed that CIRI was closely associated with the mitochondrial viscosity and HO levels. This discovery provides new insights and tools for the study of CIRI and is expected to accelerate the process of CIRI diagnosis, treatment, and drug design.
脑缺血再灌注损伤(CIRI)是脑梗死治疗过程中脑功能障碍的一个原因,与线粒体粘度和过氧化氢(HO)密切相关。然而,由于现有的与 CIRI 相关的监测工具缺乏足够的选择性和血脑屏障(BBB)穿透性,准确测量 CIRI 中的线粒体粘度和 HO 水平具有挑战性,这阻碍了对线粒体粘度和 HO 在 CIRI 中的作用的探索。为了解决这个问题,我们设计了一种可激活的荧光探针,线粒体靶向苯乙烯-喹啉-翁(),具有高选择性、线粒体靶向性和 BBB 穿透性等优异性能,用于可视化大脑中的线粒体粘度和 HO。基于探针的实时监测能力,在 CIRI 期间可视化了线粒体粘度和 HO 水平的爆发。该探针可用于监测丁基酞嗪治疗的疗效。更重要的是,体内实验进一步证实 CIRI 与线粒体粘度和 HO 水平密切相关。这一发现为 CIRI 的研究提供了新的见解和工具,并有望加速 CIRI 的诊断、治疗和药物设计进程。