质子泵抑制剂的胃黏膜保护作用与环氧化酶-2表达

目的　探讨质子泵抑制剂 (PPIs)的胃黏膜保护作用与环氧化酶 2 (COX 2 )表达的关系。方法　♂SD大鼠ig给予雷巴拉唑、奥美拉唑或兰索拉唑 5 0mg·kg-1·d-1,对照组ig给予质量分数为 0 5 %羧基纤维素 5ml·kg-1·d-1,连续 2wk。Westernblot和免疫组化检测胃黏膜COX 2表达。酶免疫方法测定胃黏膜中前列腺素E2 (PGE2 )水平 ,评价兰索拉唑和特异性COX 2抑制剂NS 3 98对乙醇所致大鼠胃黏膜损伤的影响。结果　 3种PPI均增加大鼠胃黏膜COX 2的表达。兰索拉唑呈剂量依赖性地增加胃黏膜中PGE2 含量 ,有效地减轻乙醇对胃黏膜的损伤作用。NS 3 98有效地阻断了兰索拉唑诱导的PGE2 合成及胃黏膜保护作用。结论　PPIs通过诱导胃黏膜COX 2表达 ,增加PGE2 合成而发挥胃黏膜保护作用

Protective effects of proton pump inhibitors and cyclooxygenase-2 expression in gastric mucosa

AIM To clarify the relationship between protective effects of proton pump inhibitors (PPIs) and cyclooxygenase 2 (COX 2) expression in rat gastric mucosa. METHODS Male Sprague Dawley rats were orally given one of three PPIs: rabeprazole (RP), omeprazole (OP) or lansoprazole (LP) at 50 mg·kg -1 ·d -1 for two weeks. The control group was given 0 5% carboxymethylcellulose (CMC). The animals were sacrificed and the stomachs were harvested and subjected to Western blot for COX 2 expression. The other series of rats were treated with lansoprazole at doses of 0 5, 5 and 50 mg·kg -1 ·d -1 respectively for two weeks, the level of prostaglandin (PG) E 2 in gastric mucosa and the protective action of lansoprazole against gastric injury caused by absolute ethanol were examined. The effects of a specific COX 2 inhibitor NS 398 on the PGE 2 synthesis in gastric mucosa and the mucosal protection afforded by lansoprazole were also examined. RESULTS Expression of COX 2 was strongly enhanced in gastric mucosa after two weeks administration with all of three PPIs. In the groups treated with LP (0 5,5,or 50 mg·kg -1 ), the gastric mucosal PGE 2 levels were (427±32), (483±121) and (614±82) pg·g -1 wet wt respectively ( P<0 05 vs CMC). The lesion index were (3 01%±0 38%),(2 16%±0 40%) and (0 96±0 20) % respectively ( P<0 05 vs CMC). NS 398 blocked the LP induced mucosal PGE 2 synthesis and mucosal protection. CONCLUSION The gastric mucosal protection of PPIs is related to induce COX 2 expression, increase PGE 2 synthesis in gastric mucosa.