QUASI-ELASTIC LIGHT-SCATTERING-STUDIES OF AQUEOUS BILIARY LIPID SYSTEMS - CHOLESTEROL SOLUBILIZATION AND PRECIPITATION IN MODEL BILE SOLUTIONS
QUASI-ELASTIC LIGHT-SCATTERING-STUDIES OF AQUEOUS BILIARY LIPID SYSTEMS - CHOLESTEROL SOLUBILIZATION AND PRECIPITATION IN MODEL BILE SOLUTIONS
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DOI：
10.1021/bi00271a029
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发表时间：
1983-01-01
期刊：
影响因子：
2.9
通讯作者：
CAREY, MC
中科院分区：
文献类型：
--
作者：
MAZER, NA;CAREY, MC
准弹性光散射方法用于表征牛磺酸钠（TC）、卵磷脂(L)和胆固醇（Ch）水溶液中形成的胶束聚集体和微沉淀。研究了Ch摩尔分数（XCh = 0 ~ 15%）、L/TC摩尔比（0 ~ 1.6）、温度（5 ~ 85℃）对粒径和多分散性的影响。C)和总脂质浓度（在0.15 M NaCl中为3和10 g/dl）。对于低于确定的增溶极限（XChmax）的XCh值，添加Ch对简单TC胶束的大小（第1型体系）、简单TC- l胶束与混合TC- l胶束的共存（第2型体系）以及混合盘TC- l胶束的生长（第3型体系）影响不大。对于过饱和体系（XCh/XChmax > 1），即使在XCh/XChmax = 5.3时，10 g/dl的1型体系（L/TC = 0）也以亚稳胶束溶液存在。2型体系亚稳性降低（0 < L/TC < 0.6），当XCh/XChmax超过.apprx时发生不稳定微沉淀。1.6. 在10 g/dl的混合物中，微析出物最初的大小为500-20,000 ANG，后来合并形成浮力大的宏观析出相。在3g /dl的混合物中，微沉淀更小（200- 400ang），并保持稳定，未聚结的微分散。在两种浓度下形成的微沉淀物的透射电子显微镜显示为球状非晶体结构，脂质分析显示胆固醇和卵磷脂的摩尔比（Ch/L）约为。2/1，表明微沉淀为亚稳的富含胆固醇的液晶相。在过饱和3型体系（0.6 < L/TC < 2.0）中，沉淀相是富含卵磷脂的液晶相，同样在10 g/dl体系中聚结，但形成稳定的囊泡（脂质体）结构（600-800 . ang）。半径)在3g /dl系统。结合这些实验数据，提出了模型胆系统中Ch增溶的定量热力学分析，从中严格推导出1型和2型胆系统中胆固醇一水合物增溶的自由能和焓变。此外，采用均相成核理论分析了过饱和体系中亚稳/不稳极限的来源，并推导了微相与溶液之间的界面张力。在这些实验数据和理论分析的基础上，对胆汁的结构和生理以及胆结石的发病机制提出了新的假设。特别是，研究表明，在3g /dl 2型体系中观察到的稳定微沉淀可能为胆固醇在过饱和肝胆汁中的转运提供了第二载体（除了胶束）。
Quasi-elastic light-scattering methods were used to characterize micellar aggregates and microprecipitates formed in aqueous solutions containing sodium taurocholate (TC), egg lecithin (L), and cholesterol (Ch). Particle size and polydispersity were studied as functions of Ch mole fraction (XCh = 0-15%), L/TC molar ratio (0-1.6), temperature (5-85.degree. C), and total lipid concentration (3 and 10 g/dl in 0.15 M NaCl). For XCh values below the established solubilization limits (XChmax) added Ch has little influence on the size of simple TC micelles (type 1 systems), on the coexistence of simple and mixed TC-L micelles (type 2 systems), or on the growth of mixed disc TC-L micelles (type 3 systems). For supersaturated systems (XCh/XChmax > 1), 10 g/dl type 1 systems (L/TC = 0) exist as metastable micellar solutions even at XCh/XChmax = 5.3. Metastability is decreased in type 2 systems (0 < L/TC < 0.6), and labile microprecipitation occurs when XCh/XChmax exceeds .apprx. 1.6. In 10 g/dl mixtures, the microprecipitates initially range in size from 500-20,000 ANG and later coalesce to form a buoyant macroscopic precipitate phase. In 3 g/dl mixtures, the microprecipitates are smaller (200-400 .ANG.) and remain as a stable, noncoalesced microdispersion. Transmission electron microscopy of the microprecipitates formed at both concentrations indicates a globular noncrystalline structure, and lipid analysis reveals the presence of cholesterol and lecithin in a molar ratio (Ch/L) of .apprx. 2/1, suggesting that the microprecipitates represent a metastable cholesterol-rich liquid-crystalline phase. In supersaturated type 3 systems (0.6 < L/TC < 2.0), the precipitate phase is a lecithin-rich liquid-crystalline phase which likewise coalesces in a 10 g/dl system but forms stable vesicle (liposomal) structures (600-800 .ANG. radius) in 3 g/dl systems. In conjunction with these experimental data, a quantitative thermodynamic analysis of Ch solubilization in model bile systems is presented from which rigorous deductions of the free energy and enthalpy change for solubilization of cholesterol monohydrate in type 1 and type 2 systems are obtained. In addition, homogeneous nucleation theory is used to analyze the origin of the metastable/labile limit in supersaturated systems and to deduce the interfacial tension between microprecipitates and solution. On the basis of these experimental data and theoretical analyses, new hypotheses are offered on the structure and physiology of bile and the pathogenesis of Ch gallstones. In particular, it is suggested that the stable microprecipitates observed in 3 g/dl type 2 systems may provide a secondary vehicle (in addition to micelles) for cholesterol transport in supersaturated hepatic bile.