Abstract

Background/Aims

We examined the effects of proton pump inhibitors (PPIs) on gastric antral ulcers induced by non-steroidal anti-inflammatory drugs in re-fed mice and the role of capsaicin-sensitive afferent nerves (CSANs) in the protective effects of PPIs on the antral mucosa.

Methods

Male mice were administered indomethacin after 2 h of re-feeding of diet after a 24-h fast, and gastric lesions were examined 24 h after indomethacin dosing. The effects of PPIs (lansoprazole and omeprazole), histamine H₂-receptor antagonists (H₂-RAs, famotidine, ranitidine), capsaicin and misoprostol on the formation of antral ulcers induced by indomethacin were examined. Functional ablation of CSANs was caused by pretreatment of mice with a high dose of capsaicin.

Results

Indomethacin produced lesions selectively in the gastric antrum in re-fed conditions. Formation of antral ulcers was not affected by H₂-RAs, but inhibited by PPIs, capsaicin and misoprostol. The anti-ulcer effect of lansoprazole was 30 times stronger than that of omeprazole. Antral ulcers induced by indomethacin were markedly aggravated in mice with ablated CSANs. The effects of PPIs and capsaicin on ulcer formation were inhibited by ablation of CSANs, pretreatment with a capsaicin receptor antagonist (capsazepine/ruthenium red) and an inhibitor of nitric oxide synthesis (L-NAME). However, the inhibitory effect of misoprostol was not prevented by the ablation of CSANs or drugs.

Conclusions

The results suggested that CSANs play an important role in protection of the antral mucosa and that both lansoprazole and omeprazole are capable of preventing NSAID-induced antral ulcers by activating CSANs.

中文翻译：

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质子泵抑制剂通过激活小鼠对辣椒素敏感的传入神经预防非甾体抗炎药引起的胃窦溃疡。

摘要

背景/目标

我们检查了质子泵抑制剂 (PPI) 对重新喂养小鼠非甾体抗炎药诱导的胃窦溃疡的影响以及辣椒素敏感性传入神经 (CSAN) 在 PPI 对胃窦的保护作用中的作用。粘膜。

方法

雄性小鼠在禁食 24 小时后重新喂食 2 小时后给予消炎痛，并在消炎痛给药后 24 小时检查胃部病变。检测了 PPI（兰索拉唑和奥美拉唑）、组胺 H ₂受体拮抗剂（H ₂ -RAs、法莫替丁、雷尼替丁）、辣椒素和米索前列醇对消炎痛诱导的胃窦溃疡形成的影响。CSAN 的功能性消融是由用高剂量辣椒素对小鼠进行预处理引起的。

结果

在再喂食条件下，吲哚美辛选择性地在胃窦中产生损伤。胃窦溃疡的形成不受H ₂ -RAs的影响，但受PPIs、辣椒素和米索前列醇的抑制。兰索拉唑的抗溃疡作用比奥美拉唑强30倍。在消融 CSAN 的小鼠中，消炎痛引起的胃窦溃疡明显加重。PPI 和辣椒素对溃疡形成的影响通过消融 CSAN、用辣椒素受体拮抗剂（辣椒西平/钌红）和一氧化氮合成抑制剂（L-NAME）预处理来抑制。然而，米索前列醇的抑制作用并不能通过消融 CSAN 或药物来阻止。

结论

结果表明，CSANs 在保护胃窦黏膜方面发挥着重要作用，兰索拉唑和奥美拉唑都能够通过激活 CSANs 来预防 NSAID 引起的胃窦溃疡。