Biliary proteins. Unique inhibitors of cholesterol crystal nucleation in human gallbladder bile.
Biliary proteins. Unique inhibitors of cholesterol crystal nucleation in human gallbladder bile.
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胆汁蛋白质。
DOI：
10.1172/jci111204
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Hermann,RE
中科院分区：
文献类型：
--
作者：
Holzbach,RT;Kibe,A;Thiel,E;Howell,JH;Marsh,M;Hermann,RE
与胆固醇胆石病患者的胆汁相比，过饱和的正常人胆囊胆汁中胆固醇晶体成核的起始时间持续延长。对正常人胆汁悬浮过饱和（亚稳态）的因素的研究表明，与个体胆囊胆汁样本相同的胆固醇饱和指数（CSI）和摩尔脂质组成的模型胆汁溶液具有更短的晶体成核时间，即表现出降低的亚稳定性。在向“标准”过饱和脂质组合物中添加卵磷脂、胆固醇和牛磺胆酸钠后，不饱和正常胆汁的成核时间也比同类标准模型胆汁长 3 至 15 倍。然而，当进行类似补充时，正常胆汁的总脂质提取物在成核时间上与对照模型溶液没有差异。通过凝胶色谱法对胆囊胆汁进行分级，并将洗脱的级分合并成两个级分。当与过饱和标准模型胆汁混合时，在约前 25% 的内含体积中洗脱的级分导致成核时间适度增加，约为对照值的 1.5 倍。将在所含体积的第二个25%中洗脱并含有所有胆汁脂质的级分浓缩并补充脂质至标准组合物。这些补充剂的成核时间比对照成核时间长 3-10 倍。通过不连续蔗糖梯度离心纯化的脱脂胆汁蛋白混合物与先前使用的标准组合物的纯化脂质重组。这些混合物的成核时间显着延长至与第二色谱级分相关的成核时间相同的程度。这些观察结果表明，在正常人胆囊胆汁中观察到的胆固醇晶体成核的延迟发生（抑制）是由胆汁蛋白组分中存在的因子产生的。
The onset time for cholesterol crystal nucleation of supersaturated normal human gallbladder biles is consistently prolonged when compared with biles from patients with cholesterol gallstone disease. Investigation of the factor(s) responsible for the suspended supersaturation (metastability) of normal human biles revealed that model bile solutions of cholesterol saturation index (CSI) and molar lipid composition identical to individual gallbladder bile specimens had much shorter crystal nucleation times, i.e., exhibited decreased metastability. Unsaturated normal biles, after supplementation with lecithin, cholesterol, and sodium taurocholate to a 'standard' supersaturated lipid composition, also demonstrated nucleation times three- to 15-fold longer than the comparable standard model bile. Total lipid extracts of normal biles, however, when similarly supplemented, did not differ in nucleation time from the control model solution. Gallbladder biles were fractionated by gel chromatography and the eluted fractions were pooled into two fractions. The fractions eluting in about the first 25% of the included volume when mixed with the supersaturated standard model bile induced a modest increase in nucleation time of approximately 1.5 times the control value. The fractions eluting in the second 25% of the included volume and which contained all of the bile lipids, were concentrated and supplemented with lipids to the standard composition. The nucleation times of these supplements were 3-10 times longer than the control nucleation times. Delipidated bile protein mixtures, purified by discontinuous sucrose gradient centrifugation, were recombined with purified lipids at the standard composition used previously. The nucleation times of these mixtures were significantly prolonged to the same extent as those associated with the second chromatographic fraction. These observations demonstrate that the delayed onset (inhibition) of cholesterol crystal nucleation observed in normal human gallbladder bile is produced by a factor(s) present in the biliary protein fraction.Images