Eastwood G L
Gastroenterology. 1975 Jun;68(6):1456-65.
Bile salts break the gastric mucosal barrier. To explain this, the suggestion has been made that bile salts may disrupt surface epithelial cell membranes or break the tight junctions between cells, but appropriate ultrastructural studies are lacking. We therefore instilled control and bile salt-containing solutions into the stomachs of fasted mice at pH, 1, 3, 5, AND 7. Taurocholate (pKa equals 1.8) caused mucosal injury only at pH 1, whereas glycochenodeoxycholate (pKa equals 4.2) injured the mucosa at pH 1 and 3. By electron microscopy, areas of mild mucosal injury were characterized by clumping of nuclear chromatin and loss of cytoplasmic density within surface mucous cells. The apical cell membranes and tight junctions remained intact. In areas of severe damage surface cells were ruptured but tight junctions still appeared unbroken. These studies indicate that acid pH markedly augments the damaging effects of bile salts on mouse gastric mucosa. Moreover, as an initial step in the mechanism of bile salt-induced gastric injury, the nonionized moiety of a given bile salt which exists below its pKa may be important in altering the gastric surface epithelial cell in a way which allows the ingress of bile salt and/or hydrogen ion to cause intracellular damage.
胆盐会破坏胃黏膜屏障。对此的一种解释是，胆盐可能会破坏表面上皮细胞膜或破坏细胞间的紧密连接，但缺乏适当的超微结构研究。因此，我们将对照溶液和含胆盐的溶液分别以pH值为1、3、5和7注入禁食小鼠的胃中。牛磺胆酸盐（pKa等于1.8）仅在pH值为1时引起黏膜损伤，而甘氨鹅脱氧胆酸盐（pKa等于4.2）在pH值为1和3时损伤黏膜。通过电子显微镜观察，轻度黏膜损伤区域的特征是核染色质聚集以及表面黏液细胞内细胞质密度降低。顶端细胞膜和紧密连接仍然完好无损。在严重损伤区域，表面细胞破裂，但紧密连接似乎仍然完整。这些研究表明，酸性pH值显著增强了胆盐对小鼠胃黏膜的损伤作用。此外，作为胆盐诱导胃损伤机制的第一步，给定胆盐在其pKa以下存在的非离子化部分可能在改变胃表面上皮细胞方面很重要，这种改变方式使得胆盐和/或氢离子能够进入细胞内从而造成细胞损伤。
