Divisone di Geriatria, Dipartimento di Medicina, Endocrinologia, Metabolismo e Geriatria, Università degli Studi di Modena e Reggio Emilia, Nuovo Ospedale Civile, Via Giardini 1355, Modena 41126, Italy.
Molecules. 2012 Feb 16;17(2):1939-68. doi: 10.3390/molecules17021939.
Alterations of cholesterol homeostasis represent important risk factors for atherosclerosis and cardiovascular disease. Different clinical-experimental approaches have been devised to study the metabolism of cholesterol and particularly the synthesis of bile acids, its main catabolic products. Most evidence in humans has derived from studies utilizing the administration of labeled sterols; these have several advantages over in vitro assay of enzyme activity and expression, requiring an invasive procedure such as a liver biopsy, or the determination of fecal sterols, which is cumbersome and not commonly available. Pioneering evidence with administration of radioactive sterol derivatives has allowed to characterize the alterations of cholesterol metabolism and degradation in different situations, including spontaneous disease conditions, aging, and drug treatment. Along with the classical isotope dilution methodology, other approaches were proposed, among which isotope release following radioactive substrate administration. More recently, stable isotope studies have allowed to overcome radioactivity exposure. Isotope enrichment studies during tracer infusion has allowed to characterize changes in the degradation of cholesterol via the "classical" and the "alternative" pathways of bile acid synthesis. Evidence brought by tracer studies in vivo, summarized here, provides an exceptional tool for the investigation of sterol metabolism, and integrate the studies in vitro on human tissue.
胆固醇稳态的改变是动脉粥样硬化和心血管疾病的重要危险因素。已经设计了不同的临床实验方法来研究胆固醇的代谢，特别是胆汁酸的合成，它是胆固醇的主要代谢产物。大多数来自人类的证据来自于使用标记甾醇的研究；与需要侵入性程序（如肝活检）或粪便甾醇的测定（繁琐且不常用）来测定酶活性和表达的体外测定相比，这些方法具有几个优点。放射性甾醇衍生物给药的开创性证据允许在不同情况下（包括自发性疾病、衰老和药物治疗）描述胆固醇代谢和降解的改变。除了经典的同位素稀释方法外，还提出了其他方法，其中包括放射性底物给药后同位素的释放。最近，稳定同位素研究已经能够克服放射性暴露。在示踪剂输注期间进行同位素富集研究，允许通过“经典”和胆汁酸合成的“替代”途径来描述胆固醇降解的变化。本文总结了示踪剂在体内研究中的证据，为甾醇代谢的研究提供了一个极好的工具，并将体外研究整合到人类组织中。
