Nilsson Lisa-Mari, Sjövall Jan, Strom Stephen, Bodin Karl, Nowak Greg, Einarsson Curt, Ellis Ewa
Division of Gastroenterology and Hepatology, Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, S-14186 Stockholm, Sweden.
Biochem Biophys Res Commun. 2007 Dec 28;364(4):743-7. doi: 10.1016/j.bbrc.2007.10.039. Epub 2007 Oct 15.
The conversion of cholesterol to bile acids is a key pathway for elimination of cholesterol from the body, thereby reducing the risk of arteriosclerosis. Moderate consumption of ethanol has been shown to have preventive effects on cardiovascular disease and decrease the risk of gallstone formation. In the present study primary human hepatocytes were used to investigate if ethanol affected bile acid synthesis. Hepatocytes were prepared from donor liver (n=11) and treated with ethanol, 7.7 or 50 mM, for 24 h. mRNA levels for enzymes in bile acid synthesis pathways were studied and bile acid synthesis was analyzed. Treatment with 7.7 mM ethanol increased cholic acid synthesis by 20% and treatment with 50 mM ethanol up-regulated cholic acid formation by 60%. The synthesis of cholic acid increased more than that of chenodeoxycholic acid, indicating that the classical pathway for bile acid synthesis was up-regulated. Increased bile acid levels in the cells treated with ethanol were seen after approximately 20 h. mRNA expression of CYP7A1, CYP27A1, and CYP8B1 in the hepatocytes was not affected by alcohol exposure.
胆固醇转化为胆汁酸是人体消除胆固醇的关键途径，从而降低动脉粥样硬化的风险。适度饮用乙醇已被证明对心血管疾病有预防作用，并降低胆结石形成的风险。在本研究中，使用原代人肝细胞来研究乙醇是否影响胆汁酸合成。从供体肝脏（n = 11）制备肝细胞，并用7.7或50 mM乙醇处理24小时。研究了胆汁酸合成途径中酶的mRNA水平，并分析了胆汁酸合成。用7.7 mM乙醇处理使胆酸合成增加20%，用50 mM乙醇处理使胆酸形成上调60%。胆酸的合成比鹅去氧胆酸增加得更多，表明胆汁酸合成的经典途径被上调。在用乙醇处理的细胞中，大约20小时后可见胆汁酸水平升高。肝细胞中CYP7A1、CYP27A1和CYP8B1的mRNA表达不受酒精暴露的影响。
