Watt S M, Simmonds W J
J Lipid Res. 1984 May;25(5):448-55.
The importance of the bile acid structure on mucosal uptake and lymphatic absorption of cholesterol was investigated using four different taurine-conjugated bile acids. Pure synthetic conjugates of a trihydroxy bile acid, taurocholate, and three dihydroxy bile acids, tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate were used to completely solubilize [14C]cholesterol and polar lipids for steady rate intraduodenal infusion for 8 hr in bile fistula rats. Lymph output and esterification of [14C]cholesterol and endogenous cholesterol were measured in hourly samples. A second group of bile fistula rats was given the same bile acids as the first group but without added cholesterol or other lipid, i.e., fasting lymph fistula group. Mucosal uptake of [14C]cholesterol was studied using recovery of [14C]cholesterol from lumen and mucosa after 1-hr infusions in conscious bile fistula rats. Lymph output of [14C]cholesterol was promoted more rapidly with taurocholate than with the dihydroxy conjugates and [14C]cholesterol output differed for the three groups given dihydroxy bile acids. The mass of cholesterol in lymph, measured chemically, varied in parallel with [14C]cholesterol absorption. For fasting lymph, infusion of dihydroxy bile acids failed to produce a significant change in endogenous cholesterol output when compared with rats given saline only. Taurocholate infusion markedly increased endogenous cholesterol in lymph of fasted rats. Under all conditions where cholesterol output was stimulated, the increase could be accounted for mainly as esterified cholesterol. Mucosal uptake of [14C]cholesterol during 1-hr infusions in conscious bile fistula rats was slower with the dihydroxy bile acids than with taurocholate. The results indicate the marked effect of the number and configuration of the hydroxyl groups on the solubilizing bile acid for cholesterol absorption.
利用四种不同的牛磺酸结合型胆汁酸，研究了胆汁酸结构对胆固醇黏膜摄取和淋巴吸收的重要性。使用一种三羟基胆汁酸牛磺胆酸盐以及三种二羟基胆汁酸牛磺熊去氧胆酸盐、牛磺鹅去氧胆酸盐和牛磺脱氧胆酸盐的纯合成共轭物，将[14C]胆固醇和极性脂质完全溶解，以便在胆瘘大鼠中以稳定速率进行8小时的十二指肠内输注。每小时采集样本，测量[14C]胆固醇和内源性胆固醇的淋巴输出及酯化情况。第二组胆瘘大鼠给予与第一组相同的胆汁酸，但不添加胆固醇或其他脂质，即空腹淋巴瘘组。在清醒的胆瘘大鼠中，通过1小时输注后从肠腔和黏膜中回收[14C]胆固醇，研究[14C]胆固醇的黏膜摄取情况。与二羟基共轭物相比，牛磺胆酸盐促进[14C]胆固醇的淋巴输出更快，且给予二羟基胆汁酸的三组中[14C]胆固醇输出有所不同。化学测量的淋巴中胆固醇质量与[14C]胆固醇吸收情况平行变化。对于空腹淋巴，与仅给予生理盐水的大鼠相比，输注二羟基胆汁酸未能使内源性胆固醇输出产生显著变化。输注牛磺胆酸盐显著增加了禁食大鼠淋巴中的内源性胆固醇。在所有刺激胆固醇输出的条件下，增加的部分主要可归因于酯化胆固醇。在清醒的胆瘘大鼠中，1小时输注期间，二羟基胆汁酸组的[14C]胆固醇黏膜摄取比牛磺胆酸盐组慢。结果表明羟基的数量和构型对溶解胆固醇吸收的胆汁酸有显著影响。
