| Summary: | 碩士 === 國立交通大學 === 應用化學系分子科學碩博士班 === 101 === Lipid deposits formed on the surface of coronary arteries, termed atherosclerotic plaques, can cause narrowing of lumen or completely occlude the blood stream, and may eventually lead to heart hypoxia and coronary artery heart diseases. Rupture of vulnerable atherosclerotic plaques accounts for the majority of acute cardiovascular events. Excessive hyperlipidemia induced in mice and rabbits has been extensively employed to model human atherosclerosis, but microscopic exploration of the plaques is achieved mainly postmortem. Hypercholesterolemic zebrafish induced by high-cholesterol diet (HCD) has recently been reported to be a suitable disease model to imitate the early pathological process of atherosclerosis. Herein we report the first attempt on in vivo Raman microspectroscopic investigation of vascular lipids deposited in hypercholesterolemic zebrafish. Guided with fluorescence imaging, we have successfully obtained Raman spectra of individual vascular fatty plaques, and found that the 1155 cm-1 and 1520 cm-1 Raman bands attenuated completely whereas the 1265 cm-1 and 1660 cm-1 bands were moderately declined; these two characteristic features are profoundly consistent with that measured on oxidized low-density lipoproteins (LDL). To explore pharmacological applications of our approach, we examined also HCD-fed zebrafish that were treated with a cholesterol-lowering drug. The treatment of probucol to HCD-fed zebrafish reduced the total amount of vascular lipids, and, more significantly, the percentage of oxidized lipids; 60 % of the total fatty plaques examined in this work became non-oxidized in sharply contrast with the all oxidized fatty plaques found in the control without the treatment of probucol. Further mechanistic studies show that the treatment of probucol suppressed only the formation of oxidized fatty plaque but not reversed the oxidized lipid into non-oxidized one. We anticipate our approach is extendible to investigate the efficacy of therapeutic and diet interventions to atherosclerosis.
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