Venneman Niels G, Huisman Sebastiaan J, Moschetta Antonio, vanBerge-Henegouwen Gerard P, van Erpecum Karel J
Gastrointestinal Research Unit, Department of Gastroenterology, University Medical Center Utrecht, Utrecht, The Netherlands.
Biochim Biophys Acta. 2002 Jul 11;1583(2):221-8. doi: 10.1016/s1388-1981(02)00216-0.
The hydrophilic bile salt ursodeoxycholate is frequently used to dissolve cholesterol gallstones. We have now quantitated crystallization as a function of bile salt hydrophobicity, phospholipid content, cholesterol saturation and total lipid concentration (TLCo).
Crystallization in supersaturated model biles with low phospholipid contents (left two-phase-micelles and crystal-containing-zone) was assessed during 21 days by microscopy and chemical measurement of crystal mass. For model biles with higher phospholipid contents (central three-phase-micelles, vesicles and crystal-containing-zone), lipid distribution into various phases was determined by combined ultracentrifugation-filtration-dialysis methodology (Biochim. Biophys. Acta 1532 (2001) 15-27).
In the left two-phase zone, crystal numbers and masses were highest in case of more hydrophilic bile salt composition (TUDC 100%>TC/TUDC 70%/30%>TC 100%>TC/TDC 70%/30%>TDC 100%) and decreased with increasing phospholipid contents, lower TLCo and lower cholesterol saturation index (CSI). In contrast, in the presence of vesicles (three-phase zone), crystallization decreased at increasing bile salt hydrophilicity, with concomitant increased vesicular cholesterol solubilization.
Presence of vesicular phases is a prerequisite for inhibition of cholesterol crystallization by tauroursodeoxycholate.
亲水性胆盐熊去氧胆酸常用于溶解胆固醇胆结石。我们现在已将结晶量化为胆盐疏水性、磷脂含量、胆固醇饱和度和总脂质浓度(TLCo)的函数。
通过显微镜检查和晶体质量的化学测量,在21天内评估低磷脂含量(左两相微团和含晶区)的过饱和模型胆汁中的结晶情况。对于磷脂含量较高(中间三相微团、囊泡和含晶区)的模型胆汁,通过超速离心-过滤-透析联合方法(《生物化学与生物物理学报》1532 (2001) 15 - 27)确定脂质在各相中的分布。
在左两相区,晶体数量和质量在亲水性更强的胆盐组成情况下最高(牛磺熊去氧胆酸100%>牛磺胆酸/牛磺熊去氧胆酸70%/30%>牛磺胆酸100%>牛磺胆酸/去氧胆酸70%/30%>去氧胆酸100%),并随着磷脂含量增加、TLCo降低和胆固醇饱和指数(CSI)降低而减少。相反,在存在囊泡(三相区)的情况下,随着胆盐亲水性增加,结晶减少,同时囊泡中胆固醇的溶解增加。
囊泡相的存在是牛磺熊去氧胆酸抑制胆固醇结晶的前提条件。