Ohta M, Tanoue K, Tarnawski A S, Pai R, Itani R M, Sander F C, Sugimachi K, Sarfeh I J
Department of Surgery, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Gastroenterology. 1997 Jun;112(6):1920-30. doi: 10.1053/gast.1997.v112.pm9178684.
BACKGROUND & AIMS: Portal hypertension predisposes gastric mucosa to increased injury. The aim of this study was to determine whether overexpression of constitutive nitric oxide synthase (cNOS) is responsible for increased susceptibility of portal-hypertensive (PHT) gastric mucosa to damage.
In gastric specimens from PHT and sham-operated rats, cNOS messenger RNA expression was determined by Northern blotting and cNOS protein expression by Western blotting, immunohistochemistry, and enzyme activity assay. Extent of ethanol-induced gastric mucosal necrosis, mucosal blood flow, and gastric NOS activity in PHT and sham-operated rats was determined after administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) or saline.
cNOS messenger RNA level, cNOS enzyme activity, and fluorescence signals for cNOS were increased significantly in PHT rats compared with controls. Inhibition of overexpressed cNOS by L-NAME (5 mg/kg) significantly reduced ethanol-induced mucosal necrosis and normalized blood flow in PHT gastric mucosa, whereas this dose of L-NAME significantly increased mucosal necrosis in sham-operated rats.
Portal hypertension activates the cNOS gene with overexpression of cNOS protein in endothelia of gastric mucosal vessels. Excessive NO production by overexpressed cNOS may play an important role in the increased susceptibility of PHT gastric mucosa to damage.
门静脉高压使胃黏膜更易受到损伤。本研究旨在确定组成型一氧化氮合酶（cNOS）的过表达是否导致门静脉高压（PHT）胃黏膜对损伤的易感性增加。
在PHT大鼠和假手术大鼠的胃标本中，通过Northern印迹法测定cNOS信使核糖核酸表达，通过蛋白质印迹法、免疫组织化学和酶活性测定法测定cNOS蛋白表达。在给予N（ω）-硝基-L-精氨酸甲酯（L-NAME）或生理盐水后，测定PHT大鼠和假手术大鼠乙醇诱导的胃黏膜坏死程度、黏膜血流量和胃NOS活性。
与对照组相比，PHT大鼠的cNOS信使核糖核酸水平、cNOS酶活性和cNOS荧光信号显著增加。L-NAME（5mg/kg）抑制过表达的cNOS可显著减轻乙醇诱导的PHT胃黏膜坏死并使血流量恢复正常，而该剂量的L-NAME可显著增加假手术大鼠的黏膜坏死。
门静脉高压激活cNOS基因，导致胃黏膜血管内皮细胞中cNOS蛋白过表达。过表达的cNOS产生过多的一氧化氮可能在PHT胃黏膜对损伤的易感性增加中起重要作用。
