一氧化氮合酶抑制物在胃黏膜损伤中的作用与机制

Role of nitric oxide synthase inhibitor in gastric mucosa injury and its mechanism

目的:研究一氧化氮合酶抑制物非对称性二甲基精氨酸(ADMA)在不同因素诱发的胃黏膜损伤中的作用,并初步探讨其机制。方法:用乙醇、吲哚美辛、应激诱发大鼠胃黏膜损伤模型,检测胃黏膜溃疡指数(UI),一氧化氮(NO)和ADMA水平,以及二甲基精氨酸-二甲胺水解酶(DDAH)的活性;检测幽门螺旋杆菌(Hp)处理胃黏膜上皮细胞(GES-1)细胞培养液中NO,ADMA和TNF-α水平,以及细胞中DDAH活性。结果:乙醇、吲哚美辛、应激诱发大鼠胃黏膜损伤的同时ADMA水平显著升高以及DDAH活性下降;Hp处理GES-1细胞24 h后,ADMA和TNF-α水平显著升高,DDAH活性下降;外源性ADMA也能显著升高GES-1细胞TNF-α水平。结论:ADMA是促进胃黏膜损伤的重要因子,除抑制NO生成外,还具有直接致炎作用。

Objective To explore the role of endogenous nitric oxide synthase inhibitor asym- metric dimethylarginine （ADMA） in different factors-induced gastric mucosal injury. Methods In ethanol, indomethecin and stress-induced gastric mucosa injury models, the gastric mueosal ulcer index （UI）, the level of ADMA and NO, and the activity of dimethylarginine dimethylaminohydrolase （DDAH） were determined. Cultured human gastric mucosal epithelial cells （GES-1） were treated with helicobacter pylori （Hp） or ADMA （30 μmol/L）, the concentrations of ADMA , NO and TNF-α in the conditioned medium, and the activity of DDAH in epithelial cells were determined. Results UI and the level of ADMA were increased markedly and the activity of DDAH was decreased significantly in different factors-induced gastric mucosal injury in rats. Incubation of GES-1 with Hp markedly increased the levels of ADMA and TNF-α, and decreased the activity of DDAH. ADMA （30 μmol/L） markedly increased the levels of TNF-α in cultured GES-1. Conclusion ADMA is an important factor contributing to the development of gastric mucosal injury, and such effects of ADMA may be related to inhibiting NO synthe- sis and inducing inflammatory reaction.