一氧化氮在潘托拉唑对大鼠胃黏膜损伤保护中的作用

Role of nitric oxide in pantoprazole's protective effect from gastric mucosal lesion in rats

目的:探讨一氧化氮(NO)在潘托拉唑(panto-prazole,PZ)保护大鼠胃黏膜损伤中的作用.方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予PZ(20 mg/kg),L-硝基-精氨酸甲酯(L-NAME,4 mg/kg),L-精氨酸(250 mg/kg)及D-精氨酸(250 mg/kg)静脉注射.采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),采用镉粒还原和比色法测定胃黏膜和血浆NO2-/NO3-含量,并观察了胃黏膜损伤指数(UI)、溃疡坏死组织和中性粒细胞浸润严重程度的变化.结果:与模型损伤组比,PZ组大鼠UI明显降低(P<0.01),溃疡坏死组织和中性粒细胞浸润程度明显减轻(P<0.01).预先用L-NAME处理后,PZ保护胃黏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.iv PZ,可增加GMBF、胃黏膜和血浆NO2-/NO3-,L-NAME可逆转这种作用,但对PZ抑制酸分泌作用无明显影响.结论:PZ对大鼠胃黏膜损伤保护作用与NO有关,这一作用与抑制胃酸分泌无关.

AIM： To observe the role of nitric oxide（NO） in the protective effect of pantoprazole （PZ） on gastric mucosal lesion in rats. METHODS： Before gastric mucosal lesion was made in rats by pure alcohol, PZ （20 mg/kg）, Nω-nitro-L-arginine methyl ester（L-NAME,4 mg/kg）, L-arginine（250 mg/kg） and D-arginine（250 mg/kg） were injected into the vein. Gastric mucosal blood flow（GMBF） was assessed with laser Doppler flowmetry （ LDF）, gastric mucosal and serum NO2-/NOf were measured by cadmium granulation reduction and colorimetric method and the changes of ulcer index and the severity of tissue necrosis and neutrophils infiltration were observed. RESULTS： Ulcer index in the PZ group was much lower than that in the control group（ P 〈 0.01 ） and the degree of tissue necrosis and neutrophils infiltration were much milder than those in the control group （ P 〈 0.01 ）. The protective effect of PZ 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 by D-arginine. PZ administered into the vein obviously increased GMBF, gastric mucosal and serum NO2-/NO3, which was prevented by pretreatment with L-NAME but the antisecretory effect of PZ was not affected by L-NAME. CONCLUSION： PZ has some NO mediated protective effect against gastric mucosal lesion in rats and the action of PZ against gastric acid secretion contributes little to the protective effect.