一氧化氮在恒河猴慢性结肠炎模型中的潜在作用。

Potential role of nitric oxide in a model of chronic colitis in rhesus macaques.

作者信息

Ribbons K A, Zhang X J, Thompson J H, Greenberg S S, Moore W M, Kornmeier C M, Currie M G, Lerche N, Blanchard J, Clark D A

机构信息

Department of Pediatrics, Louisiana State University Medical Center, New Orleans.

出版信息

Gastroenterology. 1995 Mar;108(3):705-11. doi: 10.1016/0016-5085(95)90442-5.

DOI:10.1016/0016-5085(95)90442-5

PMID:7533111

Abstract

BACKGROUND/AIMS: Excess nitric oxide formation, via the inducible NO synthase isoform, has been implicated in the pathogenesis of experimental and clinical inflammatory bowel disease. The aim of this study was to assess the site, enzyme source, and magnitude of NO production in juvenile rhesus macaques with idiopathic colitis.

METHODS

NO production was assessed systemically from plasma and urine levels of reactive nitrogen intermediates and locally by the formation of [3H]citrulline from [3H]arginine and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. Inducible NO synthase gene expression was assessed by reverse-transcription polymerase chain reaction.

RESULTS

Plasma and urine levels of reactive nitrogen intermediates were greater in colitic animals than in control monkeys by 13- and 5-fold, respectively. NADPH diaphorase activity in normal animals was confined to the myenteric plexus. In colitis, staining was also apparent in crypt abscesses and superficial epithelial and mucosal bands. Gene expression for inducible NO synthase was only found in colitic specimens. Colonic [3H]citrulline formation was markedly elevated in colitic specimens, and the inducible isoform accounted for 58% of total activity.

CONCLUSIONS

It is proposed that excess NO, formed via the inducible form of NO synthase, contributes to the mucosal inflammation and symptoms of this idiopathic colitis model.

摘要

背景/目的：通过诱导型一氧化氮合酶亚型生成过量一氧化氮，已被认为与实验性和临床炎症性肠病的发病机制有关。本研究的目的是评估患有特发性结肠炎的幼年恒河猴体内一氧化氮产生的部位、酶来源及程度。

方法

通过血浆和尿液中活性氮中间体的水平对一氧化氮产生进行全身评估，并通过由[3H]精氨酸生成[3H]瓜氨酸以及还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）黄递酶组织化学对一氧化氮产生进行局部评估。通过逆转录聚合酶链反应评估诱导型一氧化氮合酶基因表达。

结果

患结肠炎动物血浆和尿液中活性氮中间体的水平分别比对照猴高13倍和5倍。正常动物的NADPH黄递酶活性局限于肌间神经丛。在结肠炎中，隐窝脓肿以及浅表上皮和黏膜带也有明显染色。诱导型一氧化氮合酶的基因表达仅在结肠炎标本中发现。结肠炎标本中结肠[3H]瓜氨酸的生成明显升高，且诱导型同工型占总活性的58%。