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大鼠肠道粘蛋白对牛磺胆酸盐/磷脂酰胆碱混合微团的排阻体积效应。

Excluded volume effect of rat intestinal mucin on taurocholate/phosphatidylcholine mixed micelles.

作者信息

Wiedmann Timothy Scott, Liang Wei, Herrington Heather

机构信息

Department of Pharmaceutics, University of Minnesota, 308 Harvard St. SE, Minneapolis, MN 55455, USA.

出版信息

J Colloid Interface Sci. 2004 Feb 15;270(2):321-8. doi: 10.1016/j.jcis.2003.09.040.

Abstract

The interaction of bile salt/phospholipid mixed micelles with an intestinal mucin has been investigated to provide the foundation for the transport of ingested fat and poorly water-soluble drugs through the intestinal mucous layer. Egg phosphatidylcholine (PC) was equilibrated with sodium taurocholate (TC) to generate several series of solutions, which had different intermicellar concentrations of TC. Within each series, each solution had the same IMC and thereby micelle sizes, but varied with respect to micelle concentration. These solutions were combined with isolated rat intestinal mucin, equilibrated, and then separated by centrifugation. The supernatant and mucin pellet were assayed for PC and TC, and the diffusion coefficient of PC was measured in the supernatant by PFG-SE NMR spectroscopy. For each series, four linear relationships were found; TC supernatant concentration plotted as a function of PC supernatant concentration; TC pellet concentration plotted as a function of PC pellet concentration; TC pellet concentration plotted as a function of TC supernatant concentration; and PC pellet concentration plotted as a function of PC supernatant concentration. Theoretical analysis of these results indicated that mucin excludes from 25 to 80% of the bile salt/phospholipid mixed micelles with greater exclusion observed with larger micelle size. There is preferential association of the taurocholate with intestinal mucin, when present in the mixed micelle region of the phase diagram. The association coupled with exclusion would allow mucin to modulate the concentration of bile salt at the epithelial surface.

摘要

为了给摄入的脂肪和水溶性差的药物通过肠道黏液层的转运提供基础,人们对胆盐/磷脂混合微团与肠道黏蛋白的相互作用进行了研究。将蛋黄卵磷脂(PC)与牛磺胆酸钠(TC)平衡,以生成几个系列的溶液,这些溶液具有不同的微团间TC浓度。在每个系列中,每种溶液都有相同的微团间浓度,因此微团大小相同,但微团浓度有所不同。将这些溶液与分离出的大鼠肠道黏蛋白混合、平衡,然后通过离心分离。对上清液和黏蛋白沉淀进行PC和TC检测,并通过脉冲场梯度自旋回波核磁共振光谱法测量上清液中PC的扩散系数。对于每个系列,发现了四种线性关系;TC上清液浓度作为PC上清液浓度的函数绘制;TC沉淀浓度作为PC沉淀浓度的函数绘制;TC沉淀浓度作为TC上清液浓度的函数绘制;以及PC沉淀浓度作为PC上清液浓度的函数绘制。对这些结果的理论分析表明,黏蛋白会排斥25%至80%的胆盐/磷脂混合微团,微团尺寸越大,排斥作用越强。当牛磺胆酸盐存在于相图的混合微团区域时,它与肠道黏蛋白存在优先结合。这种结合与排斥作用相结合,将使黏蛋白能够调节上皮表面胆盐的浓度。

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