埃索美拉唑对胃黏膜的保护作用及其机制

Effect of esomeprazole on gastric mucosal lesion and its mechanism In rats

目的:探讨埃索美拉唑对大鼠胃黏膜保护的作用及其机制．方法:在乙醇诱导大鼠胃黏膜损伤前,预先给予埃索美拉唑(20 mg/kg)灌胃,L-硝基-精氨酸甲酯(L-NAME,4 mg/kg)和L-精氨酸(250 mg/ kg)iv．采用激光多普勒血流计(LDF)测定胃黏膜血流量(GMBF),镉粒还原和比色法测定胃黏膜和血浆NO_2^-/NO_3^-含量,并观察胃黏膜损伤指数(ulcer index,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,埃索美拉唑组大鼠UI明显降低(5．6±2．2 vs 25．3±2．4,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,埃索美拉唑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．向胃内灌注埃索美拉唑,可增加GMBF、胃黏膜和血浆NO_2^-/NO_3^-, L-NAME可逆转这种作用,但对埃索关拉唑抑制酸分泌作用无明显影响．结论:埃索美拉唑通过NO介导对大鼠胃黏膜损伤有重要的保护作用,而与埃索美拉唑抑制酸分泌作用无关．

AIM： To observe the protective effect of esomeprazole on gastric mucosa and its mechanism. METHODS： Before the model of gastric mucosal lesion was made by pure alcohol, esomeprazole （20 mg/kg） was intragastrically administered while Nω-nitro-L-arginine methyl ester （L-NAME, 4 mg/kg） and L-arginine （250 mg/kg） were intravenously injected into the rats. Gastric mucosal blood flow （GMBF） was measured with laser Doppler flowmetry （LDF）, while gastric mucosal and serum NO^-2/NO^-3 levels were examined by cadmium granulation reduction and colorimetric method. The changes of ulcer index and the severity of tissue necrosis and neutrophil infiltration were also observed. RESULTS： The ulcer index was significantly lower in the rats with esomeprazole pretreatment than that in the model rats （5.6 ± 2.2 vs 25.3 ± 2.4, P 〈 0.01）, and the degree of tissue necrosis and neutrophil infiltration were also much milder （P〈 0.01）. Prior administration of L-NAME obviously inhibited the protective effect of esomeprazole was on gastric mucosa, but the inhibition was alleviated by L-arginine. Esomeprazole increased GMBF and gastric mucosal or serum NO^-2/NO^-3 level, which was suppressed by L-NAME. Esomeprazole had no marked effect on the secretion of gastric acid. CONCLUSION： Esomeprazole can protect gastric mucosa against alcohol-induced injury, which is mediated by nitric oxide.