Wang Li, Zhou Yuan, Peng Jun, Zhang Zhe, Jiang De-Jian, Li Yuan-Jian
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No.110 Xiang-Ya Road, Changsha 410078, China.
Can J Physiol Pharmacol. 2008 Mar;86(3):97-104. doi: 10.1139/y08-003.
To explore the role of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in gastric mucosal injury, 3 models of gastric mucosal injury induced by ethanol, indomethacin, or cold stress were used in rats. The cultured human gastric mucosal epithelial cell line GES-1 infected by Helicobacter pylori (Hp) was selected to mimic human gastric mucosal injury. Gastric mucosal ulcer index (UI), levels of ADMA and NO, and activity of dimethylarginine dimethylaminohydrolase (DDAH) were determined in the mucosal injury models; in Hp-infected or ADMA-treated GES-1 cells, levels of ADMA, NO, and TNF-alpha and activity of DDAH were measured. The results showed that UI and levels of ADMA were markedly increased and accompanied by significantly decreased DDAH activity in the mucosal injury models. Incubation of GES-1 cells with Hp increased levels of TNF-alpha and ADMA and decreased activity of DDAH. Administration of ADMA also increased levels of TNF-alpha. The results suggest that ADMA plays an important role in facilitating gastric mucosal injury, an effect which is associated with inhibiting NO synthesis and inducing inflammatory reaction.
为探讨内源性一氧化氮合酶（NOS）抑制剂不对称二甲基精氨酸（ADMA）在胃黏膜损伤中的作用，在大鼠中采用了乙醇、吲哚美辛或冷应激诱导的3种胃黏膜损伤模型。选用幽门螺杆菌（Hp）感染的人胃黏膜上皮细胞系GES-1进行培养，以模拟人胃黏膜损伤。测定黏膜损伤模型中的胃黏膜溃疡指数（UI）、ADMA和NO水平以及二甲基精氨酸二甲胺水解酶（DDAH）活性；在Hp感染或ADMA处理的GES-1细胞中，检测ADMA、NO和TNF-α水平以及DDAH活性。结果显示，在黏膜损伤模型中，UI和ADMA水平显著升高，同时DDAH活性明显降低。用Hp孵育GES-1细胞可增加TNF-α和ADMA水平，并降低DDAH活性。给予ADMA也会增加TNF-α水平。结果表明，ADMA在促进胃黏膜损伤中起重要作用，这种作用与抑制NO合成和诱导炎症反应有关。
