Kaviani A, Ohta M, Itani R, Sander F, Tarnawski A S, Sarfeh I J
Department of Surgery, Department of Veterans Affairs Medical Center, Long Beach, Calif, USA.
J Gastrointest Surg. 1997 Jul-Aug;1(4):371-6. doi: 10.1016/s1091-255x(97)80059-5.
Increased expression of both nitric oxide synthase (NOS) and tumor necrosis factor-alpha (TNF-alpha) have been implicated in the hyperdynamic circulation of portal hypertension. Since overexpression of these proteins would affect gastric mucosal defenses, which are impaired in portal hypertension, we examined the expression and interrelationships of TNF-alpha and NOS in the gastric mucosa of portal hypertensive rats. Following staged portal vein ligation, gastric strips from portal hypertensive rats were incubated in organ culture medium with or without TNF-alpha antibody. The expression of TNF-alpha and NOS mRNAs was assessed by reverse transcription-polymerase chain reaction (RT-PCR) at baseline and after 1, 2, and 6 hours of incubation. RT-PCR demonstrated a threefold increase in inducible NOS mRNA and a 50% increase in TNF-alpha mRNA expression at baseline in portal hypertensive animals as compared to sham-operated animals. In tissue incubated with TNF-alpha neutralizing antibody, inducible NOS mRNA expression was significantly decreased by 40%, 70%, and 80% after 1, 2, and 6 hours, respectively. Since increased TNF-alpha and NOS production could potentially impair gastric mucosal defenses, our findings suggest a major role for these proteins in the development of portal hypertensive gastropathy.
一氧化氮合酶（NOS）和肿瘤坏死因子-α（TNF-α）的表达增加与门静脉高压的高动力循环有关。由于这些蛋白质的过度表达会影响胃黏膜防御功能，而胃黏膜防御功能在门静脉高压时受损，因此我们研究了门静脉高压大鼠胃黏膜中TNF-α和NOS的表达及相互关系。在进行分期门静脉结扎后，将门静脉高压大鼠的胃条在含有或不含有TNF-α抗体的器官培养基中孵育。在基线以及孵育1、2和6小时后，通过逆转录-聚合酶链反应（RT-PCR）评估TNF-α和NOS mRNA的表达。与假手术动物相比，RT-PCR显示门静脉高压动物在基线时诱导型NOS mRNA增加了三倍，TNF-α mRNA表达增加了50%。在用TNF-α中和抗体孵育的组织中，诱导型NOS mRNA表达在1、2和6小时后分别显著降低了40%、70%和80%。由于TNF-α和NOS产生增加可能会损害胃黏膜防御功能，我们的研究结果表明这些蛋白质在门静脉高压性胃病的发生发展中起主要作用。
