Castañeda A A, Denning J W, Chang L, Mercer D W
Department of Surgery, University of Texas-Houston Medical School, Houston, Texas, 77030, USA.
J Surg Res. 1999 Jun 15;84(2):174-9. doi: 10.1006/jsre.1999.5637.
Nitric oxide from constitutive nitric oxide synthase (NOS) augments gastric mucosal blood flow and is important in mucosal defense. However, the function of the inducible isoform of NOS (iNOS) in the gastric mucosa remains to be fully elucidated. This study was done to examine the role of iNOS in gastric mucosal blood flow and gastric injury following endotoxemia. Conscious rats were given intraperitoneal saline or lipopolysaccharide (LPS, 5 or 20 mg/kg). Five hours later, rats were anesthetized, a laparotomy made, gastric fluid aspirated, and 3 ml of 20% ethanol introduced into the forestomach. Rats were sacrificed 10 min later for assessment of macroscopic injury (mm2) to the gastric mucosa. Other rats did not receive 20% ethanol, but instead, gastric mucosal blood flow was determined with laser Doppler, followed by sacrifice and removal of stomachs for determination of gastric mucosal iNOS immunoreactivity (Western immunoblot). Lipopolysaccharide dose dependently increased gastric injury, decreased gastric mucosal blood flow, and increased gastric mucosal iNOS immunoreactivity compared to rats receiving saline. In additional experiments and using a similar protocol, intraperitoneal administration of aminoguanidine (45 mg/kg), an iNOS inhibitor, reversed lipopolysaccharide-induced gastric injury and restored gastric mucosal blood flow to baseline, whereas the nonselective NOS inhibitor, NG-nitro-l-arginine methyl ester (5 mg/kg) did not. Taken together, these data suggest that upregulation of iNOS is in part responsible for the detrimental effects of LPS on the gastric mucosa, possibly from a reduction in gastric mucosal blood flow.
组成型一氧化氮合酶（NOS）产生的一氧化氮可增加胃黏膜血流量，对黏膜防御至关重要。然而，胃黏膜中诱导型一氧化氮合酶（iNOS）的功能仍有待充分阐明。本研究旨在探讨内毒素血症后iNOS在胃黏膜血流量和胃损伤中的作用。给清醒大鼠腹腔注射生理盐水或脂多糖（LPS，5或20 mg/kg）。5小时后，将大鼠麻醉，进行剖腹手术，抽吸胃液，并向胃体部注入3 ml 20%乙醇。10分钟后处死大鼠，评估胃黏膜的宏观损伤面积（mm²）。其他大鼠未接受20%乙醇，但用激光多普勒测定胃黏膜血流量，随后处死并取出胃，测定胃黏膜iNOS免疫反应性（Western免疫印迹法）。与接受生理盐水的大鼠相比，脂多糖剂量依赖性地增加胃损伤、降低胃黏膜血流量并增加胃黏膜iNOS免疫反应性。在额外的实验中，采用类似方案，腹腔注射iNOS抑制剂氨基胍（45 mg/kg）可逆转脂多糖诱导的胃损伤，并使胃黏膜血流量恢复至基线水平，而非选择性NOS抑制剂NG-硝基-L-精氨酸甲酯（5 mg/kg）则无此作用。综上所述，这些数据表明iNOS的上调部分导致了LPS对胃黏膜的有害影响，可能是由于胃黏膜血流量减少所致。
