Takeuchi K, Okada M, Niida H, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Dig Dis Sci. 1990 Aug;35(8):984-92. doi: 10.1007/BF01537247.
Pathogenesis of indomethacin-induced gastric lesions was investigated in the rat by measuring lesions, gastric motility, and terminal blood glucose levels and correlating them with each other. Subcutaneously administered indomethacin (3-25 mg/kg) dose-dependently produced lesions in the stomach with concomitant gastric hypermotility and reduction of blood glucose levels. When the lesion score and the motility were plotted against terminal glucose levels, a highly significant relationship was found among these three factors (P less than 0.01). Gastric lesions and hypermotility induced by indomethacin (25 mg/kg) were suppressed significantly by 16,16-dmPGE2 (10 micrograms/kg) with no effect on the glucose levels, while intravenous infusion of glucose (25% w/w, 1.4 ml/hr) prevented these responses and restored the reduced glucose levels above the basal values. In addition, both 16,16-dmPGE2 and glucose infusion afforded a significant protection against gastric lesions induced by indomethacin even in the acid-perfused stomach (150 mM HCl). These results confirmed gastric hypermotility as a key element in the pathogenesis of indomethacin-induced lesions and further suggested that indomethacin may sensitive gastric contractility through glycoprivic receptors by inducing hypoglycemia and PG deficiency.
通过测量大鼠胃损伤、胃动力和末梢血糖水平并相互关联，研究了吲哚美辛诱导胃损伤的发病机制。皮下注射吲哚美辛（3 - 25毫克/千克）剂量依赖性地导致胃损伤，同时伴有胃动力亢进和血糖水平降低。当将损伤评分和胃动力与末梢葡萄糖水平作图时，发现这三个因素之间存在高度显著的关系（P小于0.01）。16,16 - dmPGE2（10微克/千克）可显著抑制吲哚美辛（25毫克/千克）诱导的胃损伤和胃动力亢进，而对葡萄糖水平无影响，同时静脉输注葡萄糖（25% w/w，1.4毫升/小时）可预防这些反应并使降低的葡萄糖水平恢复至基础值以上。此外，即使在酸灌注胃（150 mM HCl）中，16,16 - dmPGE2和葡萄糖输注对吲哚美辛诱导的胃损伤均提供了显著保护。这些结果证实胃动力亢进是吲哚美辛诱导损伤发病机制中的关键因素，并进一步表明吲哚美辛可能通过诱导低血糖和前列腺素缺乏，通过糖缺乏受体使胃收缩性敏感化。
