Konturek S J, Brzozowski T, Piastucki I, Radecki T
Digestion. 1983;28(2):125-31. doi: 10.1159/000198975.
This study was designed to determine the influence of acetazolamide, a potent inhibitor of carbonic anhydrase, on the formation of gastric mucosal lesions induced by acidified aspirin (ASA) or absolute ethanol and on gastric cytoprotection induced by prostaglandin E2 (PGE2). Acetazolamide prevented dose-dependently ethanol-induced gastric lesions and this effect was accompanied by an increased biosynthesis of mucosal PGs, indicating that endogenous PGs may be involved in cytoprotection by acetazolamide. This is supported by the finding that acetazolamide failed to affect gastric ulcerations produced by acidified ASA when mucosal PG biosynthesis was almost completely suppressed. Pretreatment with acetazolamide did not influence the protective action of PGE2 on ethanol-induced mucosal lesions and only slightly inhibited the protective effect of PGE2 on ASA-induced gastric ulcerations. This study indicates that: (1) acetazolamide prevents ethanol- but not ASA-induced gastric mucosal lesions probably via stimulation of PG biosynthesis and (2) gastric alkaline secretion, mediated by carbonic anhydrase, is probably not an essential mechanism responsible for this cytoprotection induced by PGE2.
本研究旨在确定强效碳酸酐酶抑制剂乙酰唑胺对酸化阿司匹林（ASA）或无水乙醇诱导的胃黏膜损伤形成的影响，以及对前列腺素E2（PGE2）诱导的胃细胞保护作用的影响。乙酰唑胺能剂量依赖性地预防乙醇诱导的胃损伤，且这一作用伴随着黏膜前列腺素生物合成的增加，表明内源性前列腺素可能参与了乙酰唑胺的细胞保护作用。当黏膜前列腺素生物合成几乎完全被抑制时，乙酰唑胺未能影响酸化ASA产生的胃溃疡，这一发现支持了上述观点。乙酰唑胺预处理不影响PGE2对乙醇诱导的黏膜损伤的保护作用，且仅轻微抑制PGE2对ASA诱导的胃溃疡的保护作用。本研究表明：（1）乙酰唑胺可能通过刺激前列腺素生物合成来预防乙醇而非ASA诱导的胃黏膜损伤；（2）由碳酸酐酶介导的胃碱性分泌可能不是PGE2诱导的这种细胞保护作用的关键机制。
