Cho C H, Chen S M, Chen S W, Chow C K, Lai K H, Pfeiffer C J
Digestion. 1984;29(1):5-11. doi: 10.1159/000199001.
The present experiment demonstrated that relatively high doses of acetazolamide (100 and 200 mg/kg s.c.) induced severe gastric hemorrhagic ulceration in rats. This ulceration was aggravated by oral administration of HC1, but was inhibited by NaHCO3. Further, the severity of ulceration was also decreased by pretreatment with methysergide, chlorpheniramine, or cimetidine. These protective effects were affirmed by an increase in serotonin and histamine released from the stomach after acetazolamide treatment. Acetazolamide injection also increased the protein level, but reduced the sialic acid content in the gastric secretion, indicating that the gastric mucosal barrier may have been damaged. Prostaglandin E2 content of the gastric mucosa was not affected by the drug; however, carbonic anhydrase activity was markedly reduced in a dose-dependent manner. Thus, it is suggested that the ulceration induced by acetazolamide is mainly due to the inhibition of carbonic anhydrase activity and mucus secretion. The increases in serotonin and histamine released may also have been contributing factors for gastric ulcer formation.
本实验表明，相对高剂量的乙酰唑胺（100和200mg/kg皮下注射）可诱导大鼠出现严重的胃出血性溃疡。口服盐酸可加重这种溃疡，但碳酸氢钠可抑制。此外，用麦角新碱、氯苯那敏或西咪替丁预处理也可降低溃疡的严重程度。乙酰唑胺治疗后胃中5-羟色胺和组胺释放增加，证实了这些保护作用。注射乙酰唑胺还可提高蛋白质水平，但降低胃分泌物中的唾液酸含量，表明胃黏膜屏障可能已受损。胃黏膜中前列腺素E2含量不受该药物影响；然而，碳酸酐酶活性呈剂量依赖性显著降低。因此，提示乙酰唑胺诱导的溃疡主要是由于碳酸酐酶活性和黏液分泌受到抑制。5-羟色胺和组胺释放增加也可能是胃溃疡形成的促成因素。
