质子泵抑制剂对胃粘膜环氧化酶—2表达的影响

Effects of proton pump inhibitors on gastric mucosal expression of cyclooxygenase2

目的探讨质子泵抑制剂(PPI)对大鼠胃粘膜环氧化酶—2(COX-2)表达的影响。方法 1.大鼠经胃管给予Rabeprazole(雷巴拉唑),Lansoprazole(兰索拉唑),Pantoprazol(潘妥拉唑),50mg/kg,对照组给予0.5％碳氧甲基纤维素(carboxymethyllulose,CMC),5ml/kg每天一次,连续14天,应用免疫印渍检测胃粘膜COX-1和COX-2表达水平。2.连续14天给予0.5mg/kg,5mg/kg或50mg/kg的兰索拉唑,对照组给予0.5％CMC,应用酶免疫测定法(EIA)检测大鼠胃粘膜中前列腺素E_2(PGE_2)含量,并观察兰索拉唑对酒精所致急件胃粘膜损伤的保护作用.3.特异性COX-2抑制剂(NS-398)对大鼠胃粘膜PGE_2合成及胃粘膜保护作用的影响.结果 1.PPI显著地增加大鼠胃粘膜COX-2的表达水平而不影响COX-1的表达。2.胃粘膜中PGE_2含量,对照组为266±81pg/gwet tissue:0.5mg/kg,5mg/kg 50mg/kg的兰索拉唑组分別为427±32 pg/g,483±121 pg/g(p<0.05 vs.对照组),614±82pg/g(p<0.01 vs.对照组).3.酒精对大鼠胃粘膜的损伤指数.对照组为3.78±0.29％,0.5mg/kg～50mg/kg的兰索拉唑组分别为3.01±0.38％(p<0.05、vs.对照组).2.16±0.40％(p<0.005 vs.对照组)和0.96±0.20％(p<0.005 vs.对照组)。4.NS398有效地阻断了兰索拉唑诱导的PGE_2合成及胃粘膜保护作用。结论 PPI通过诱导胃粘膜COX-2表达,增加PGE_2合成而发挥胃粘膜保护作用。

Objective To clarify whether proton pump inhibitors (PPIs) stimulate Cyclooxygenase-2(COX-2) expression in rat gastric mucosa.Methods Male Sprague Dawley rats were orally given one of three PPIs: rabeprazole, Iansoprazole or pantoprazole at 50 mg/kg once daily for fourteen days.The control group was given 0.5% carboxymethylcellulose (CMC). The animals were sacrificed and the stomachs were harvested and sbjected to Western blotting for COX-1 and COX-2 expression.The other series of rats were treated with Iansoprazole at doses of 0.5. 5 and 50mg/lg respectively for fourteen days, the level of prostaglandin (PG) E2 in gastric mucosa and the protective action of lansoprazole against gastric damange 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 lansoprazde were also examined.Results Expression of COX-2 was strongly enhanced in gastric mucosa after fourteen days administration with all of three PPIs.The gastric mucosal PGE, level in the CMC treated group was 266±81pg/g wet tissue.In the groups treated with lansoprazole (0.5,5.or 50mg/kg), the gastric mucosal PGE2 levels were 427±32 pg/g,483±121 pg/g(p<0.05 vs.CMC) and 614±82 pg/g(p<0.01 vs.CMC) respectively.Lansoprazole also reduced gastric damage caused by ethanol in a dose dependent manner (3.01±0.38%. 2.16±0.40% and 0.96 ±0.20% vs. 3.78 0.29% in control group).A specific inhibitor of COX- 2 blocked the lansoprazole induced mucosal PGE2 synthesis and mucosal protection. Conclusion The gastric mucosal protection of PPIs is related to induce COX-2 expression, increase PGE2 synthesis in gastric mucosa.