In Situ Lipidomic Analysis of Nonalcoholic Fatty Liver by Cluster TOF-SIMS Imaging
In Situ Lipidomic Analysis of Nonalcoholic Fatty Liver by Cluster TOF-SIMS Imaging
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DOI：
10.1021/ac900045m
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发表时间：
2009-04-15
影响因子：
7.4
通讯作者：
Laprevote, Olivier
中科院分区：
文献类型：
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作者：
Debois, Delphine;Bralet, Marie-Pierre;Laprevote, Olivier
质谱成像已被用于映射几个患有非酒精性脂肪性肝病的患者的肝活检。这种脂肪变性的特征是三酰基甘油和二酰基甘油在肝脏中的积累。使用飞行时间二次离子质谱（TOF-SIMS）与铋簇离子源，它已经可以映射脂质原位在微米尺度，并同时表征其分子分布在肝脏切片。与对照肝脏相比，在脂肪肝的脂肪变性区域观察到三酰基甘油、二酰基甘油、单酰基甘油、脂肪酸的积累，伴随肉豆蔻酸的出现，以及维生素E的急剧消耗和胆固醇的选择性大空泡定位。这些离子种类集中在具有几微米大小的小囊泡中。此外，在仔细检查离子图像后，发现脂质定位的非常细微的差异，取决于二酰基甘油和脂肪酸的烷基酸链长度。最后，TOF-SIMS揭示了正常人肝脏中的脂质分区和与脂肪肝区域中检测到的脂质非常相似的脂质积累，通过对连续组织切片进行的组织学对照，脂肪肝区域未被表征为脂肪变性区域。
Mass spectrometry imaging has been used to map liver biopsies of several patients suffering from nonalcoholic fatty liver disease. This steatosis is characterized by an accumulation of triacylglycerols and diacylglycerols in the liver. Using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) with a bismuth cluster ion source, it has been possible to map lipids in situ at the micrometer scale and to simultaneously characterize their molecular distribution on liver sections. Accumulation of triacylglycerols, diacylglycerols, monoacylglycerols, fatty acids, with the apparition of myristic acid, together with a dramatic depletion of vitamin E and a selective macrovacuolar localization of cholesterol are observed in steatosis areas of fatty livers compared to control livers. These ion species are concentrated in small vesicles having a size of a few micrometers. Moreover, very fine differences in lipid localizations, depending on alkyl acid chain lengths of diacylglycerols and fatty acids, have been found after careful scrutiny of the ion images. Finally, TOF-SIMS has revealed lipid zonation in the normal human liver and accumulation of very similar lipids to those detected in areas of the fatty livers, which are not characterized as steatotic ones by the histological control performed on serial tissue sections.