Origin of oxysterols in hepatic bile of patients with biliary infection
Origin of oxysterols in hepatic bile of patients with biliary infection
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DOI：
10.1111/j.1572-0241.2003.07703.x
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发表时间：
2003-10
影响因子：
9.8
通讯作者：
Tadashi Yoshida;Y. Matsuzaki;W. Haigh;Sugano Fukushima;K. Ikezawa;N. Tanaka;S. Lee
中科院分区：
文献类型：
--
作者：
Tadashi Yoshida;Y. Matsuzaki;W. Haigh;Sugano Fukushima;K. Ikezawa;N. Tanaka;S. Lee
氧化固醇在体内普遍存在，除了作为代谢调节剂外，还是潜在的细胞毒性剂。虽然胆汁中含有高浓度的胆固醇，但胆汁中的氧化固醇浓度和感染对氧化固醇水平的影响尚未测量，也没有研究它们的来源。本研究的目的是确定是否感染的胆道与胆汁中氧化固醇的浓度增加，如果是这样，其中氧化固醇表现出显着的changes.METHODS：肝胆汁从8例胆道疾病通过鼻胆管导管。结果：肝胆汁中含有7-α-羟基胆固醇、7-β-羟基胆固醇、胆甾烷-3-β，5-α，6-β-三醇、25-羟基胆固醇、26-羟基胆固醇、7-酮基胆固醇和7-α-羟基-4-胆甾烯-3-酮。肝胆汁中总氧化固醇的范围为0.133 μmol/L ~ 7.748 μmol/L（1.47 ± 2.55 μmol/L）。感染胆汁中的7-α-羟基胆固醇和7-β-羟基胆固醇水平升高（分别为14.2 ± 15.1 × 10−3%胆固醇vs 1.9 ± 0.5 × 10−3%胆固醇，p < 0.05; 22.0 ± 25.0 × 10−3%胆固醇vs 1.6 ± 1.2 × 10− 3%胆固醇，p < 0.05）。血清C-反应蛋白水平与胆汁中7-α-羟基胆固醇（R= 0.948）、7-β-羟基胆固醇（R= 0.976）、胆甾烷-3-β，5-α，6-β-三醇（R= 0.823）、7-α-羟基-4-胆甾烯-3-酮（R= 0.846）和7-酮基胆固醇（R= 0.973）水平呈正相关。在胆结石中发现了不同的氧化固醇，主要是3-酮-胆甾-4-烯（干重的624 ± 316 ppm），3-酮-胆甾-4，6-二烯（240 ± 329 ppm）和7-酮-胆固醇（77 ± 81 ppm）。孵育的人白细胞与模型胆汁中存在的细菌脂多糖导致甾醇组合物的变化，包括oxysterols.CONCLUSIONS增加：我们已经确定和量化的oxysterols从未感染和感染的人肝胆汁和胆结石和胆囊胆汁。胆汁感染可能通过活化白细胞产生活性氧参与胆汁中氧固醇的生物合成。
OBJECTIVES:Oxysterols are ubiquitous in the body and are potential cytotoxic agents in addition to being metabolic regulators. Although bile contains high concentrations of cholesterol, oxysterol concentrations in bile and the effect of infection on oxysterol levels have not been measured, nor has their origin been studied. The purpose of this study was to determine if infection of the biliary tract was associated with increased concentrations of oxysterols in the bile and, if so, which oxysterols showed a significant change.METHODS:Hepatic bile was obtained from eight patients with biliary tract disease by means of a naso-biliary catheter. Oxysterols were extracted and purified by solid-phase extraction, derivatized and measured by gas chromatography–mass spectrometry.RESULTS:The following were quantified in hepatic bile: 7-α-hydroxycholesterol, 7-β-hydroxycholesterol, cholestan-3-beta,5-alpha,6-β-triol, 25-hydroxycholesterol, 26-hydroxycholesterol, 7-ketocholesterol, and 7-α-hydroxy-4-cholesten-3-one. Total oxysterols in hepatic bile ranged from 0.133 μmol/L to 7.748 μmol/L (1.47 ± 2.55 μmol/L). Levels of 7-α-hydroxycholesterol and 7-β-hydroxycholesterol were increased in infected bile (14.2 ± 15.1 × 10−3% of cholesterol vs 1.9 ± 0.5 × 10−3% of cholesterol, p < 0.05, and 22.0 ± 25.0 × 10−3% of cholesterol vs 1.6 ± 1.2 × 10−3% of cholesterol, p < 0.05, respectively). Serum C-reactive protein levels correlated positively with biliary levels of 7-α-hydroxycholesterol (R= 0.948), 7-β-hydroxycholesterol (R= 0.976), cholestan-3-beta,5-alpha,6-β-triol (R= 0.823), 7-α-hydroxy-4-cholesten-3-one (R= 0.846,) and 7-ketocholesterol (R= 0.973). Different oxysterols were found in gallstones, chiefly 3-keto-cholest-4-ene (624 ± 316 parts per million [ppm] of dry weight), 3-keto-cholesta-4,6-diene (240 ± 329 ppm) and 7-keto-cholesterol (77 ± 81 ppm). Incubation of human leukocytes with model bile in the presence of bacterial lipopolysaccharide resulted in changes in sterol composition, including increases in oxysterols.CONCLUSIONS:We have identified and quantified oxysterols from uninfected and infected human hepatic bile and from gallstones and gallbladder bile. Biliary infection may be involved in the biogenesis of oxysterols in bile through the production of reactive oxygen species from activated leukocytes.