Armstrong D, Rytina E R, Murphy G M, Dowling R H
Gastroenterology Unit, UMDS of Guy's Hospital, London, UK.
Dig Dis Sci. 1994 Feb;39(2):327-39. doi: 10.1007/BF02090205.
To determine the acute gastrotoxicity of refluxed duodenal contents, an ex vivo rat gastric chamber was used to study mucosal damage produced by conjugated and unconjugated human bile acids and lysolecithin at neutral and acidic pH; the effects of trypsin, human duodenal aspirate, and combinations of chenodeoxycholic acid, lecithin, and lysolecithin were also studied. At neutral pH, all bile acids except tauroursodeoxycholic acid, caused dose-dependent falls in mucosal potential difference and losses of mucosal nucleic acid into the chamber fluid, indicating mucosal damage. The di-alpha-hydroxy bile acids, deoxycholic and chenodeoxycholic acids, were more gastrotoxic than cholic and ursodeoxycholic acids, and all unconjugated bile acids were more toxic than their conjugated species, none of which produced damage at concentrations below 2.0 mM. For all but the taurine conjugates, bile acid-induced changes in potential difference were lower at acidic then at neutral pH. Lysolecithin gastrotoxicity, comparable at neutral pH to that of chenodeoxycholic acid, was also reduced at acidic pH. Lecithin decreased the gastrotoxicity of chenodeoxycholic acid and lysolecithin. Trypsin produced no damage, and the gastrotoxicity of human duodenal aspirate was unaffected by prior heat inactivation of pancreatic enzymes.
为了确定反流十二指肠内容物的急性胃毒性，使用离体大鼠胃腔研究了在中性和酸性pH值下共轭和非共轭人胆汁酸及溶血卵磷脂对黏膜的损伤；还研究了胰蛋白酶、人十二指肠抽吸物以及鹅去氧胆酸、卵磷脂和溶血卵磷脂组合的影响。在中性pH值下，除牛磺熊去氧胆酸外，所有胆汁酸均导致黏膜电位差呈剂量依赖性下降以及黏膜核酸流失到腔液中，表明存在黏膜损伤。二α-羟基胆汁酸，即脱氧胆酸和鹅去氧胆酸，比胆酸和熊去氧胆酸的胃毒性更强，并且所有非共轭胆汁酸比其共轭形式毒性更大，在浓度低于2.0 mM时，它们均未造成损伤。对于除牛磺酸共轭物外的所有物质，胆汁酸诱导的电位差变化在酸性pH值下低于中性pH值。溶血卵磷脂的胃毒性在中性pH值下与鹅去氧胆酸相当，在酸性pH值下也有所降低。卵磷脂降低了鹅去氧胆酸和溶血卵磷脂的胃毒性。胰蛋白酶未造成损伤，人十二指肠抽吸物的胃毒性不受胰腺酶预先热灭活的影响。
