NO在兰索拉唑对大鼠胃粘膜保护中作用的研究

Role of nitric oxide in the protective effect of lansoprazole on the gastric mucosa in rats

目的 :探讨一氧化氮 (NO)在兰索拉唑对大鼠胃粘膜保护中的作用。 方法 :在乙醇诱导大鼠胃粘膜损伤前 ,预先给予兰索拉唑 (2 0 m g/ kg)灌胃 ,L-硝基 -精氨酸甲酯 (L- NAME,4m g/ kg)、L-精氨酸 (2 5 0 mg/ kg) ,D-精氨酸 (2 5 0 m g/ kg)静脉注射。测定胃粘膜血流量 (GMBF)、胃液 p H、胃粘膜和血浆的 NO2 - / NO3- ,并观察了胃粘膜损伤指数 (ulcer index,UI)、溃疡坏死组织和中性粒细胞浸润程度的变化。结果 :与模型损伤组相比 ,兰索拉唑组大鼠 U I明显降低 (P<0 .0 1) ,溃疡坏死组织和中性粒细胞浸润程度明显减轻 (P<0 .0 1)。用 L- NAME处理后 ,兰索拉唑保护胃粘膜损伤作用明显减弱 ;L- NAME抑制作用可被 L-精氨酸拮抗 ,而不被 D-精氨酸拮抗。向胃内灌注兰索拉唑 ,可增加 GMBF、胃粘膜和血浆的 NO2 - / NO3- ,L- NAME可逆转这种作用 ,但对兰索拉唑抑制酸分泌作用无明显影响。 结论 :兰索拉唑对大鼠胃粘膜保护作用与 NO有关 ,而兰索拉唑抑制酸分泌作用与 NO无关。

Objective: To observe the role of nitric oxide(NO)in the protective effect of lansoprazole on the gastric mucosa in rats. Methods:Before gastric mucosal lesion were made in rats by pure alcohol,lansoprazole (20 mg/kg)was administered into the gastric chamber and Nω nitro L arginine methyl ester( L NAME,4 mg/kg), L arginine(250 mg/kg) and D arginine(250 mg/kg) was injected into the vein . Gastric mucosal blood flow(GMBF), pH of gastric juice,gastric mucosal and serum NO 2 -/NO 3 - were measured; The changes of ulcer index, the degree of necrotic tissues and neutrophils submersion were observed. Results:Ulcer index of the lansoprazole group was much lower than that of the control group( P <0.01),and the degree of necrotic tissues and neutrophils submersion the lansoprazole group was much milder than that of the control group( P <0.01). The protective effect of lansoprazole was significantly decreased by prior administration of L NAME. The inhibitory effect of L NAME was antagonized by prior administration of L arginine,but not D arginine. Lansoprazole administered directly into the gastric chamber obviously increased GMBF,gastric mucosal and serum NO 2 -/NO 3 - , which was prevented by pretreatment with L NAME, but the antisecretory effect of lansoprazole was not affected by L NAME. Conclusion:NO is involved in the mucosal protection of lansoprazole,but is not involved in the antisecretory action of lansoprazole. [