Duane W C, Wiegand D M
J Clin Invest. 1980 Nov;66(5):1044-9. doi: 10.1172/JCI109932.
Bile salts disrupt a functional "gastric mucosal barrier" increasing net forward-diffusion (+) of Na+ and back-diffusion (-) of H+. Studying canine Heidenhain pouches, we attempted to distinguish between two possible mechanisms for this effect: (a) mucosal uptake of bile salt with subsequent cellular injury or (b) dissolution of mucosal lipids by intralumenal bile salt. A 10 mM mixture of six conjugated bile salts simulating the proportions found in human bile induced net Na+ flux of 15.5 +/- 3.2 and net H+ flux of -9.9 +/- 3.3 mueq/min. This change was accompanied by an increase in phospholipid efflux out of gastric mucosa from a base-line value of 13.2 +/- 2.7 to 54.8 +/- 2.8 nmol/min (P < 0.001) and an increase in cholesterol efflux from 11.7 +/- 3.8 to 36.3 +/- 3.2 nmol/min (P < 0.001). Saturation with lecithin (25 mM) and cholesterol (50 mM) blocked disruption of the gastric mucosal barrier by bile salt (Na+ flux - 1.2 +/- 0.9, H+ flux 0.6 +/- 1.8 mueq/min). A 10 mM solution of taurodehydrocholate, a bile salt that does not form micelles, induced no net Na+ (-0.3 +/- 0.8) or H+ flux (-0.7 +/- 1.4) and did not increase efflux of phospholipid (11.3 +/- 1.7) or cholesterol (10.4 +/- 2.0) over base line. Bile salt was absorbed from the mixture of six conjugates at 752 +/- 85 nmol/min. Addition of subsaturation amounts of lecithin (4 mM) reduced bile salt absorption three fold to 252 +/- 57 (P < 0.001), but abnormal Na+ flux (14.1 +/- 3.4) and H+ flux (-15.6 +/- 3.5) persisted. Taurodehydrocholate was absorbed to an intermediate extent (467 +/- 116). Dissolution of mucosal lipids is apparently the mechanism by which bile salt disrupts the gastric mucosal barrier, and presumably at least one mechanism by which bile salt can injure the gastric mucosa.
胆盐会破坏功能性的“胃黏膜屏障”，增加钠离子的净正向扩散（+）和氢离子的反向扩散（-）。在对犬海登海因小胃的研究中，我们试图区分这种效应的两种可能机制：（a）胆盐被黏膜摄取，随后导致细胞损伤；（b）腔内胆盐溶解黏膜脂质。一种模拟人胆汁中比例的10 mM六种结合胆盐混合物，可诱导钠离子净通量为15.5±3.2，氢离子净通量为-9.9±3.3微当量/分钟。这种变化伴随着胃黏膜中磷脂流出量从基线值13.2±2.7增加到54.8±2.8纳摩尔/分钟（P<0.001），以及胆固醇流出量从11.7±3.8增加到36.3±3.2纳摩尔/分钟（P<0.001）。用卵磷脂（25 mM）和胆固醇（50 mM）饱和可阻止胆盐对胃黏膜屏障的破坏（钠离子通量-1.2±0.9，氢离子通量0.6±1.8微当量/分钟）。一种不形成微胶粒的胆盐牛磺去氢胆酸盐的10 mM溶液，不会诱导净钠离子通量（-0.3±0.8）或氢离子通量（-0.7±1.4），且不会使磷脂（11.3±1.7）或胆固醇（10.4±2.0）的流出量超过基线。胆盐从六种结合物的混合物中以752±85纳摩尔/分钟的速度被吸收。加入亚饱和量的卵磷脂（4 mM）可使胆盐吸收减少三倍至252±57（P<0.001），但异常的钠离子通量（14.1±3.4）和氢离子通量（-15.6±3.5）仍然存在。牛磺去氢胆酸盐的吸收程度处于中等水平（467±116）。黏膜脂质的溶解显然是胆盐破坏胃黏膜屏障——大概也是胆盐损伤胃黏膜的至少一种机制。
