Goto H, Sugiyama S, Tsukamoto Y, Kuroiwa M, Ohara A, Hoshino H, Nakazawa S, Ozawa T
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Arzneimittelforschung. 1991 Jun;41(6):635-7.
This study was designed to clarify effects of proton pump inhibitors, E-3810(2-([4-(3-methoxypropoxy)-3methylpyridine-2-yl]methyl- sulfinyl)-1H-benzimidazol sodium salt) and omeprazole (CAS 73590-58-6), on water immersion stress-induced gastric ulcers in relation to mucosal prostaglandins (PGs) and leukotrienes (LTs). Mucosal PGs were measured by high performance liquid chromatography (HPLC). In untreated rats, 4 kinds of PGs, i.e., 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and PGD2 were detected in gastric mucosa, but no LTs were detected. Water immersion stress for 6 h caused severe hemorrhagic lesions in the fundic portion and, concomitantly, significant decreases in mucosal PG levels. On the other hand, LTC4 and LTD4 were detected after 6 h stress treatment, though LTB4 and LTE4 were not detected throughout the experiments. Peptide-LT (the sum of LTC4 and LTD4) levels were 23.5 +/- 3.2 ng/g tissue 6 h after water immersion stress. Administration of 20 mg/kg of E-3810 or 20 mg/kg of omeprazole mitigated gastric lesions and increases in the mucosal peptide-LT levels, but dit not improve the decrease in mucosal PGs.
本研究旨在阐明质子泵抑制剂E-3810（2-([4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基-亚磺酰基)-1H-苯并咪唑钠盐）和奥美拉唑（CAS 73590-58-6）对水浸应激诱导的胃溃疡的影响，及其与黏膜前列腺素（PGs）和白三烯（LTs）的关系。采用高效液相色谱法（HPLC）测定黏膜PGs。在未处理的大鼠胃黏膜中检测到4种PGs，即6-酮-前列腺素F1α、前列腺素F2α、前列腺素E2和前列腺素D2，但未检测到LTs。6小时的水浸应激导致胃底部出现严重的出血性病变，同时黏膜PG水平显著降低。另一方面，应激处理6小时后检测到白三烯C4和白三烯D4，而在整个实验过程中未检测到白三烯B4和白三烯E4。水浸应激6小时后，肽类白三烯（白三烯C4和白三烯D4之和）水平为23.5±3.2 ng/g组织。给予20 mg/kg的E-3810或20 mg/kg的奥美拉唑可减轻胃部病变并降低黏膜肽类白三烯水平，但不能改善黏膜PGs的降低。
