Brzozowski T, Drozdowicz D, Majka J, Polonczyk-Pytko J, Konturek S J
Institute of Physiology, Academy of Medicine, Krakow, Poland.
J Physiol Pharmacol. 1991 Jun;42(2):181-93.
Polyamines have been shown to stimulate cellular growth and differentiation, though their role in the prevention of acute gastric lesion induced by various noxious agents has been little studied. Epidermal growth factor (EGF) exhibits gastroprotective and ulcer healing properties due to its potent mitogenic and growth promoting action. This study was designed to compare the gastroprotective effects of spermine and EGF against gastric damage induced by absolute ethanol, acidified aspirin and stress and to determine the role of endogenous polyamines in EGF-induced gastroprotection. Spermine and EGF significantly reduced the lesions induced by all three ulcerogens. Oral administration of spermine or subcutaneous infusion of EGF in 24 h fasted rats with chronic gastric fistula resulted in similar inhibition of gastric acid and pepsin secretion. Pretreatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, did not affect ethanol lesions, but reversed the protective effect EGF but not spermine against ethanol. This finding indicates that polyamines mediate, at least in part, EGF-induced gastroprotection. In tests with oral administration of aminoguanidine that is known to suppress the activity of diamino-oxidase (DAO) and to inhibit the degradation of polyamines, EGF showed a markedly enhanced gastroprotective activity against ethanol damage. Since indomethacin failed to affect the gastroprotective effects of spermine and EGF and neither of these agents influenced the mucosal generation of PGE2 in intact or injured gastric mucosa, we conclude that prostaglandins are not the major factors in spermine- and EGF-induced gastroprotection. This study demonstrates that polyamines are highly effective against gastric lesions induced by various ulcerogens and that they act as primary mediators of EGF-induced gastroprotection.
多胺已被证明能刺激细胞生长和分化，不过它们在预防由各种有害因子诱导的急性胃损伤中的作用鲜有研究。表皮生长因子（EGF）因其强大的促有丝分裂和生长促进作用而具有胃保护和溃疡愈合特性。本研究旨在比较精胺和EGF对无水乙醇、酸化阿司匹林及应激诱导的胃损伤的胃保护作用，并确定内源性多胺在EGF诱导的胃保护中的作用。精胺和EGF均能显著减轻由所有这三种致溃疡剂诱导的损伤。对患有慢性胃瘘的禁食24小时大鼠口服精胺或皮下输注EGF，会导致对胃酸和胃蛋白酶分泌的类似抑制。用二氟甲基鸟氨酸（DFMO）进行预处理，DFMO是鸟氨酸脱羧酶（ODC，多胺生物合成中的关键酶）的不可逆抑制剂，它不影响乙醇诱导的损伤，但会逆转EGF而非精胺对乙醇的保护作用。这一发现表明，多胺至少部分介导了EGF诱导的胃保护作用。在口服氨基胍的试验中，已知氨基胍可抑制二胺氧化酶（DAO）的活性并抑制多胺的降解，EGF对乙醇损伤显示出明显增强的胃保护活性。由于吲哚美辛未能影响精胺和EGF的胃保护作用，且这两种药物均未影响完整或受损胃黏膜中PGE2的黏膜生成，我们得出结论，前列腺素不是精胺和EGF诱导的胃保护作用的主要因素。本研究表明，多胺对各种致溃疡剂诱导的胃损伤非常有效，并且它们作为EGF诱导的胃保护作用的主要介质发挥作用。
