背景:质子泵抑制剂(PPI)可预防阿司匹林相关的胃和十二指肠粘膜损伤。然而,长期使用PPI会导致各种不良反应,如胃息肉和肠嗜铬细胞样增生。目前研究表明,上述不良反应主要与高胃泌素血症有关。我们研究了奥美拉唑的低频给药是否可以有效修复阿司匹林引起的粘膜损伤并降低长期使用PPI相关的胃泌素水平的升高。
方法:Sprague-Dawley大鼠分为4个治疗组:每日服用阿司匹林,每日阿司匹林和奥美拉唑每天一次(qd),每日阿司匹林和奥美拉唑每隔一天一次(qod),每日阿司匹林和奥美拉唑每三天一次(1/d3)。喂食15天后,收集血样,处死大鼠的胃进行宏观观察,组织学,和免疫组织化学研究。此外,在临床实践中,阿司匹林引起的消化性溃疡患者每隔一天服用一次标准剂量的奥美拉唑(20mg).两个月后,进行胃镜检查以检查溃疡的愈合情况。
结果:奥美拉唑qd和奥美拉唑qod给药都能有效预防阿司匹林引起的胃溃疡,两组在抑制壁细胞分泌胃酸和细胞凋亡方面无显著差异。然而,奥美拉唑1/d3不能完全预防阿司匹林引起的胃粘膜损伤。值得注意的是,胃泌素水平,奥美拉唑qd组的细胞增殖能力和胆囊收缩素B受体表达明显高于奥美拉唑qod组。在临床工作中,由阿司匹林引起的消化性溃疡患者每隔一天给予标准剂量的奥美拉唑,两个月后他们的溃疡就痊愈了,如胃镜观察。
结论:奥美拉唑隔日一次可有效预防阿司匹林引起的消化性溃疡,降低高胃泌素血症,这可能会减少PPI治疗的长期不良反应。
BACKGROUND: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs.
METHODS: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and
omeprazole once every other day (qod), and daily aspirin and
omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers.
RESULTS: Both the
omeprazole qd and
omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However,
omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the
omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy.
CONCLUSIONS: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.