Ma L, Chow J Y, Cho C H
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, China.
Life Sci. 1998;62(3):257-66. doi: 10.1016/s0024-3205(97)01104-1.
Cigarette smoking is associated with peptic ulceration in humans. A mechanistic study of the potentiating effects of cigarette smoking on acetic acid-induced gastric ulceration in rats was hence performed. Rats were exposed to 0, 2 or 4% of cigarette smoke for three 1-hr periods during the 24 hr starvation before ulcer induction. Cigarette smoke exposure potentiated ulcer formation which was accompanied by a reduction of gastric blood flow at the ulcer base and ulcer margin. Further studies showed that cigarette smoke exposure alone did not cause any macroscopic injury in the stomach but significantly decreased the basal gastric blood flow in a concentration-dependent manner, which was coupled with an increase in mucosal xanthine oxidase (XO) activity. Pretreatment with allopurinol (Allo, 5 mg/kg, i.v.), a XO inhibitor, partially prevented the potentiating effect of cigarette smoke exposure on ulcer formation and also significantly improved the gastric blood flow. Ulcer induction itself dramatically increased constitutive nitric oxide synthase (cNOS) activity and prostaglandin E2 (PGE2) level in the gastric mucosa. However, the increment of cNOS activity but not PGE2 level was markedly attenuated by cigarette smoke exposure. Sodium nitroprusside (SNP, 25 or 50 microg/kg, i.v.), a nitric oxide (NO) donor, completely abolished the potentiating effect of cigarette smoke exposure on ulcer formation and also reversed the adverse effect on gastric blood flow. Thus, XO activation and cNOS reduction in the gastric mucosa are closely associated with the potentiating action of cigarette smoke exposure on ulcer formation in rats.
吸烟与人类消化性溃疡有关。因此，进行了一项关于吸烟对大鼠乙酸诱导的胃溃疡的增强作用的机制研究。在诱导溃疡前的24小时饥饿期间，将大鼠暴露于0%、2%或4%的香烟烟雾中，持续三个1小时的时间段。暴露于香烟烟雾会增强溃疡形成，同时溃疡底部和边缘的胃血流量减少。进一步的研究表明，单独暴露于香烟烟雾不会在胃中造成任何肉眼可见的损伤，但会以浓度依赖的方式显著降低基础胃血流量，同时伴有粘膜黄嘌呤氧化酶（XO）活性增加。用XO抑制剂别嘌呤醇（Allo，5mg/kg，静脉注射）预处理可部分预防香烟烟雾暴露对溃疡形成的增强作用，并显著改善胃血流量。诱导溃疡本身会显著增加胃粘膜中组成型一氧化氮合酶（cNOS）活性和前列腺素E2（PGE2）水平。然而，香烟烟雾暴露会显著减弱cNOS活性的增加，但不会减弱PGE2水平的增加。一氧化氮（NO）供体硝普钠（SNP，25或50μg/kg，静脉注射）完全消除了香烟烟雾暴露对溃疡形成的增强作用，并逆转了对胃血流量的不利影响。因此，胃粘膜中XO的激活和cNOS的减少与香烟烟雾暴露对大鼠溃疡形成的增强作用密切相关。
