Mercer D W, Castaneda A A, Denning J W, Chang L, Russell D H
Department of Surgery, University of Texas Medical School, Houston, Texas 77030, USA.
Am J Physiol. 1998 Sep;275(3):G449-59. doi: 10.1152/ajpgi.1998.275.3.G449.
The expression and function of inducible nitric oxide synthase (iNOS) in the stomach is unclear. This study assessed the effects of endotoxin on rat gastric iNOS expression and its role in gastric injury from luminal irritants. In conscious rats, a 5-h treatment with intraperitoneal lipopolysaccharide (LPS; 1-20 mg/kg) dose dependently increased gastric mucosal iNOS immunoreactivity and increased gastric luminal nitrate and nitrite accumulation (Griess reaction). LPS also increased gastric luminal fluid accumulation and reduced macroscopic gastric injury from orogastric acidified ethanol. Aminoguanidine (45 mg/kg) did not prevent LPS-induced gastroprotection or gastric fluid accumulation. NG-nitro-L-arginine methyl ester increased gastric luminal fluid and caused macroscopic gastric injury when given with LPS. Using an anesthetized preparation followed by removal of luminal fluid, LPS reduced gastric mucosal blood flow and exacerbated gastric injury from either acidified ethanol or acidified taurocholate, an effect that was negated by aminoguanidine. These data indicate that in conscious rats, the gastroprotective effect of endotoxin is dependent on constitutive NOS but not iNOS activity. However, the inducible isoform participates in the ability of endotoxin to exacerbate gastric injury from luminal irritants in the anesthetized rat.
诱导型一氧化氮合酶（iNOS）在胃中的表达及功能尚不清楚。本研究评估了内毒素对大鼠胃iNOS表达的影响及其在管腔刺激物所致胃损伤中的作用。在清醒大鼠中，腹腔注射脂多糖（LPS；1 - 20 mg/kg）5小时，剂量依赖性地增加胃黏膜iNOS免疫反应性，并增加胃腔内硝酸盐和亚硝酸盐积累（格里斯反应）。LPS还增加胃腔内液体蓄积，并减轻经口给予酸化乙醇所致的肉眼可见的胃损伤。氨基胍（45 mg/kg）不能预防LPS诱导的胃保护作用或胃液体蓄积。LPS给药时，NG-硝基-L-精氨酸甲酯增加胃腔内液体并导致肉眼可见的胃损伤。使用麻醉制备方法并去除管腔内液体后，LPS降低胃黏膜血流量，并加重酸化乙醇或酸化牛磺胆酸盐所致的胃损伤，氨基胍可消除这一作用。这些数据表明，在清醒大鼠中，内毒素的胃保护作用依赖于组成型一氧化氮合酶而非iNOS活性。然而，诱导型同工型参与了内毒素加重麻醉大鼠管腔刺激物所致胃损伤的能力。
