Satoh H, Guth P H, Grossman M I
Gastroenterology. 1983 Mar;84(3):483-9.
Indomethacin produces mucosal lesions in both the gastric antrum and small intestine in rats refed for 1 h after a 24-h fast. This study was designed to determine the role of bacteria in the formation of the antral lesions. A mixture of antibiotics (bacitracin, neomycin, and polymyxin B) prevented the antral lesions as well as intestinal lesions. The antibiotics also decreased the gastric corpus lesions induced by indomethacin in the fasted rat. Under a germ-free condition, indomethacin did not produce severe lesions in the small intestine of the refed rat but provoked many lesions in the antrum of the refed rat and in the corpus of the fasted rat. Corpus lesions induced by indomethacin in the fasted rat were decreased markedly by neomycin and slightly by polymyxin B, but not by bacitracin. Corpus lesions produced by an absolute ethanol, however, were prevented by each of the antibiotics. The inhibitory effect of neomycin on the corpus lesions was not blocked by pretreatment with indomethacin. In pylorus-ligated rats, neomycin did not decrease gastric acid secretion. The concentration of nonprotein sulfhydryls in the gastric mucosa was not altered by the treatment with neomycin. The antibiotic solutions were hypotonic. It is concluded that (a) bacteria are not important in the formation of antral and corpus lesions induced by indomethacin, and (b) antibiotics prevent gastric ulceration not by its antibacterial action, but by a "cytoprotective" action. The mechanism is unknown, but it may be different from that of antisecretory drugs, prostaglandins, mild irritants, hypertonic solutions, and sulfhydryl compounds.
禁食24小时后再喂食1小时的大鼠，吲哚美辛会在胃窦和小肠产生黏膜损伤。本研究旨在确定细菌在胃窦损伤形成中的作用。抗生素混合物（杆菌肽、新霉素和多粘菌素B）可预防胃窦损伤以及肠道损伤。这些抗生素还可减轻禁食大鼠中由吲哚美辛诱导的胃体损伤。在无菌条件下，吲哚美辛不会在再喂食大鼠的小肠中产生严重损伤，但会在再喂食大鼠的胃窦和禁食大鼠的胃体中引发许多损伤。禁食大鼠中由吲哚美辛诱导的胃体损伤，新霉素可使其明显减轻，多粘菌素B可使其稍有减轻，但杆菌肽则无此作用。然而，绝对乙醇所致的胃体损伤，每种抗生素均可预防。新霉素对胃体损伤的抑制作用不会因吲哚美辛预处理而被阻断。在幽门结扎的大鼠中，新霉素不会降低胃酸分泌。新霉素处理不会改变胃黏膜中非蛋白巯基的浓度。抗生素溶液为低渗溶液。结论为：（a）细菌在吲哚美辛诱导的胃窦和胃体损伤形成中并不重要；（b）抗生素预防胃溃疡并非通过其抗菌作用，而是通过一种“细胞保护”作用。其机制尚不清楚，但可能与抗分泌药物、前列腺素、轻度刺激剂、高渗溶液和巯基化合物的机制不同。
