MECHANISMS OF BILE SALT MEDIATED CHOLESTEROL ABSORPTION

来自其他实验室和我们实验室的数据表明， 胆盐在胆固醇的吸收中起重要作用， 小肠及其作用超出了溶解 胆固醇我们最近还在体内证明， 磷脂酰胆碱（PC）的吸收抑制了 胆固醇通过小肠。根据这些初步观察， 我们假设：I：肠细胞对胆固醇的摄取是 受胆汁盐胶束组成和结构的影响; 二.肠细胞对胆固醇的摄取是通过结合 存在于刷状缘膜中的蛋白质。为了检验这些假设， 淋巴瘘大鼠以及体外制备的小 将使用肠粘膜。具体目标1.初步研究从 我们的实验室证明，在具有完整肠肝的大鼠中， 牛磺熊去氧胆酸盐（UDC-Tau）胆汁循环 抑制大鼠小肠对胆固醇的摄取。获得 更好地了解UDC-tau如何抑制肠 胆固醇吸收，我们将确定如何变化的摩尔 UDC-tau/牛磺胆酸盐（C-tau）的比例影响肠吸收 胆瘘大鼠的胆固醇水平。具体目标2.定义如何 胆汁中胆汁酸结构的改变会影响肠道 胆固醇、其他膳食脂质和可溶性脂的吸收 淋巴瘘大鼠的维生素。具体目标3.我们将决定 磷脂酰胆碱（PC）分子的组成部分是重要的， 小肠对胆固醇吸收的抑制作用及其机制 甘油三酯（TG）或其消化产物逆转这种抑制。 具体目标4.我们将确定是否摄入胆固醇从 混合胶束的肠细胞是蛋白质介导的， 特别是，如果UDC-tau对胆固醇摄取的抑制作用是 蛋白质介导的，是CD 36参与这一过程。

Previous data from other laboratories as well as ours demonstrated that bile salts play an important role in the absorption of cholesterol by the small intestine and its role extends beyond the solubilization of cholesterol. We have also demonstrated recently in vivo that the absorption of phosphatidylcholine (PC) inhibits the absorption of cholesterol by the small intestine. Based on these initial observations, we hypothesize that: I: The uptake of cholesterol by the enterocytes is influenced by the composition and structure of the bile salt micelle; II. The uptake of cholesterol by the enterocytes is mediated by binding proteins present in the brush border membrane. To test these hypotheses, lymph fistula rats as well as in vitro preparations of the small intestinal mucosa will be used. SPECIFIC AIM 1. Preliminary study from our laboratory demonstrated that in rats with intact enterohepatic circulation of bile slats, tauroursodeoxycholate (UDC-Tau) still inhibits the uptake of cholesterol by the rat small intestine. To gain a better understanding of the mechanism of how UDC-tau inhibits intestinal cholesterol absorption, we will determine how variations in the molar ratio of UDC-tau/taurocholate (C-tau) affects the intestinal absorption of cholesterol in bile fistula rats. SPECIFIC AIM 2. To define how alterations in the bile in the bile acid structure affect the intestinal absorption of cholesterol, other dietary lipids, and lipid soluble vitamins in lymph fistula rats. SPECIFIC AIM 3. We will determine which component of the phosphatidylcholine (PC) molecule is important in its inhibition of cholesterol absorption by the small intestine and how triglyceride (TG), or its digestion products, reverse this inhibition. SPECIFIC AIM 4. We will determine if the uptake of cholesterol from mixed micelles by the enterocytes is protein-mediated and more specifically, if the inhibition of cholesterol uptake by UDC-tau is protein-mediated and is CD36 involved with this process.