Molecular imaging of ischemia and reperfusion in vivo with mitochondrial autofluorescence

Hsueh Han Lu, Yao Ming Wu, Wei Tien Chang, Teng Luo, Yi Cyun Yang, Hung Der Cho, Ian Liau*

*此作品的通信作者

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23 引文 斯高帕斯(Scopus)

摘要

Ischemia and reperfusion (IR) injury constitutes a pivotal mechanism of tissue damage in pathological conditions such as stroke, myocardial infarction, vascular surgery, and organ transplant. Imaging or monitoring of the change of an organ at a molecular level in real time during IR is essential to improve our understanding of the underlying pathophysiology and to guide therapeutic strategies. Herein, we report molecular imaging of a rat model of hepatic IR with the autofluorescence of mitochondrial flavins. We demonstrate a revelation of the histological characteristics of a liver in vivo with no exogenous stain and show that intravital autofluorescent images exhibited a distinctive spatiotemporal variation during IR. The autofluorescence decayed rapidly from the baseline immediately after 20-min ischemia (approximately 30% decrease in 5 min) but recovered gradually during reperfusion (to approximately 99% of the baseline 9 min after the onset of reperfusion). The autofluorescent images acquired during reperfusion correlated strongly with the reperfused blood flow. We show further that the autofluorescence was produced predominantly from mitochondria, and the distinctive autofluorescent variation during IR was mechanically linked to the altered balance between the flavins in the oxidized and reduced forms residing in the mitochondrial electron-transport chain. Our approach opens an unprecedented route to interrogate the deoxygenation and reoxygenation of mitochondria, the machinery central to the pathophysiology of IR injury, with great molecular specificity and spatiotemporal resolution and can be prospectively translated into a medical device capable of molecular imaging. We envisage that the realization thereof should shed new light on clinical diagnostics and therapeutic interventions targeting IR injuries of not only the liver but also other vital organs including the brain and heart.

原文English
頁(從 - 到)5024-5031
頁數8
期刊Analytical chemistry
86
發行號10
DOIs
出版狀態Published - 20 5月 2014

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