Ohta Y, Kobayashi T, Nishida K, Ishiguro I
Department of Biochemistry, School of Medicine, Fujita Health University, Aichi, Japan.
Dig Dis Sci. 1997 Jun;42(6):1221-32. doi: 10.1023/a:1018854107623.
The relationship between the changes of active oxygen metabolism and blood flow and the formation, progression, and recovery of lesions was examined in the gastric mucosa of rats treated once with compound 48/80, a mast cell degranulator. Gastric mucosal lesions appeared 0.5 hr after compound 48/80 treatment, became worst at 3 hr, and recovered fairly well at 12 hr. Increases in gastric mucosal lipid peroxide content and xanthine oxidase and myeloperoxidase activities and decreases in gastric mucosal vitamin E and hexosamine contents and Se-dependent glutathione peroxidase activity occurred with the formation and progression of gastric mucosal lesions. These changes were attenuated with the recovery of the lesion. Gastric mucosal nonprotein SH content decreased with the formation of gastric mucosal lesions, and this decreased SH content returned to near the original level with lesion progression. No changes in gastric mucosal superoxide dismutase and catalase activities occurred with the formation, progression, and recovery of gastric mucosal lesions. Gastric mucosal blood flow decreased with the formation of gastric mucosal lesions, and this decreased blood flow recovered with lesion progression. Serum serotonin concentration, an index of mast cell degranulation, increased with the formation of gastric mucosal lesions, and this increased serotonin level was attenuated with lesion progression and recovery. Pretreatment with ketotifen, a connective tissue mast cell stabilizer, prevented the formation of gastric mucosal lesions, the increases of gastric mucosal lipid peroxide content, xanthine oxidase and myeloperoxidase activities, and serum serotonin level; and the decreases of gastric mucosal nonprotein SH content, glutathione peroxidase activity, and blood flow found at 0.5 hr after compound 48/80 treatment. These results indicate that the changes of gastric mucosal active oxygen metabolism and blood flow are closely related to the formation, progression, and recovery of gastric mucosal lesions in rats with a single compound 48/80 treatment. The present results also suggest that this compound 48/80-induced gastric mucosal injury could be a kind of ischemia-reperfusion-induced injury occurring through degranulation of connective tissue mast cells.
在经肥大细胞脱颗粒剂化合物48/80单次处理的大鼠胃黏膜中，研究了活性氧代谢和血流变化与损伤的形成、发展及恢复之间的关系。化合物48/80处理后0.5小时出现胃黏膜损伤，3小时时损伤最严重，12小时时恢复良好。随着胃黏膜损伤的形成和发展，胃黏膜脂质过氧化物含量、黄嘌呤氧化酶和髓过氧化物酶活性增加，胃黏膜维生素E和己糖胺含量以及硒依赖性谷胱甘肽过氧化物酶活性降低。随着损伤的恢复，这些变化减弱。胃黏膜非蛋白巯基含量随着胃黏膜损伤的形成而降低，且随着损伤发展，降低的巯基含量恢复至接近原始水平。胃黏膜超氧化物歧化酶和过氧化氢酶活性在胃黏膜损伤的形成、发展及恢复过程中未发生变化。胃黏膜血流随着胃黏膜损伤的形成而减少，且随着损伤发展血流恢复。血清5-羟色胺浓度作为肥大细胞脱颗粒的指标，随着胃黏膜损伤的形成而升高，且随着损伤发展和恢复，升高的5-羟色胺水平减弱。用结缔组织肥大细胞稳定剂酮替芬预处理可预防胃黏膜损伤的形成、胃黏膜脂质过氧化物含量的增加、黄嘌呤氧化酶和髓过氧化物酶活性以及血清5-羟色胺水平的升高；还可预防化合物48/80处理后0.5小时出现的胃黏膜非蛋白巯基含量、谷胱甘肽过氧化物酶活性和血流的降低。这些结果表明，单次化合物48/80处理的大鼠胃黏膜活性氧代谢和血流变化与胃黏膜损伤的形成、发展及恢复密切相关。目前的结果还表明，这种化合物48/80诱导的胃黏膜损伤可能是一种通过结缔组织肥大细胞脱颗粒发生的缺血-再灌注诱导损伤。
