Konturek P K, Brzozowski T, Konturek S J, Dembiński A
Institute of Physiology, Academy of Medicine, Krakow, Poland.
Gastroenterology. 1990 Dec;99(6):1607-15. doi: 10.1016/0016-5085(90)90464-c.
Epidermal growth factor promotes the growth of and protects gastric mucosa against various ulcerogens, including stress, but little is known about its role in the pathogenesis of stress ulcerations. In this study, Wistar rats with intact and resected salivary glands were exposed to water-immersion and restraint stress. During 2-14 hours of water-immersion restraint stress, the formation of gastric ulcerations increased progressively and the duration of stress was accompanied by a decrease in DNA synthesis in the gastric mucosa. Following sialoadenectomy, a significant increase in the number of stress ulcerations and further reduction in DNA synthesis were observed. Exogenous epidermal growth factor and dimethyl prostaglandin E2 significantly reduced the ulcerations in the stressed rats with intact salivary glands, but this reduction was significantly less pronounced after sialoadenectomy. Water-immersion restraint stress also resulted in about 50% reduction in mucosal prostaglandin E2 generation, and the pretreatment with indomethacin, which suppressed prostaglandin E2 by about 90%, almost doubled the number of stress ulcerations and abolished the gastro-protective effect of exogenous epidermal growth factor (but not dimethyl prostaglandin E2) against the stress lesions. An inhibition of ornithine decarboxylase activity by difluoromethyl ornithine also augmented stress-induced ulcerogenesis and abolished the protective action of epidermal growth factor while the administration of spermine almost completely prevented stress ulcerations in rats both without and with pretreatment with difluoromethylornithine. Water-immersion restraint stress also significantly reduced mucosal content of glutathione. Cysteamine increased tissue glutathione and reduced stress ulcerations but N-ethylmaleimide, an sulfhydryl blocker, decreased mucosal content of glutathione without affecting the stress ulcerations. This study indicates that the stress ulcers are accompanied by the reduction in mucosal synthesis of DNA, prostaglandin, and glutathione and that the presence of salivary glands attenuates the stress ulcerogenesis probably by releasing epidermal growth factor which acts, in part, by enhancing ornithine decarboxylase activity, mucosal growth, and prostaglandin and glutathione formation.
表皮生长因子可促进胃黏膜生长，并保护其免受包括应激在内的各种致溃疡因素的侵害，但对于其在应激性溃疡发病机制中的作用却知之甚少。在本研究中，将唾液腺完整和切除的Wistar大鼠暴露于水浸束缚应激环境中。在2 - 14小时的水浸束缚应激期间，胃溃疡的形成逐渐增加，且应激持续时间伴随着胃黏膜中DNA合成的减少。唾液腺切除术后，观察到应激性溃疡的数量显著增加，DNA合成进一步减少。外源性表皮生长因子和二甲基前列腺素E2可显著减少唾液腺完整的应激大鼠的溃疡形成，但唾液腺切除术后这种减少明显不那么显著。水浸束缚应激还导致黏膜前列腺素E2生成减少约50%，用吲哚美辛预处理抑制前列腺素E2约90%，几乎使应激性溃疡的数量增加一倍，并消除了外源性表皮生长因子（但不是二甲基前列腺素E2）对应激性损伤的胃保护作用。用二氟甲基鸟氨酸抑制鸟氨酸脱羧酶活性也会增强应激诱导的溃疡形成，并消除表皮生长因子的保护作用，而给予精胺几乎完全预防了未用和用二氟甲基鸟氨酸预处理的大鼠的应激性溃疡。水浸束缚应激还显著降低了黏膜中谷胱甘肽的含量。半胱胺增加了组织中的谷胱甘肽并减少了应激性溃疡，但巯基阻断剂N - 乙基马来酰亚胺降低了黏膜中谷胱甘肽的含量，而不影响应激性溃疡。本研究表明，应激性溃疡伴随着黏膜中DNA、前列腺素和谷胱甘肽合成的减少，唾液腺的存在可能通过释放表皮生长因子来减轻应激性溃疡的形成，表皮生长因子部分通过增强鸟氨酸脱羧酶活性、黏膜生长以及前列腺素和谷胱甘肽的形成来发挥作用。
