THE SELECTIVE BENEFICIAL-EFFECTS OF NITRIC-OXIDE INHIBITION IN EXPERIMENTAL COLITIS
THE SELECTIVE BENEFICIAL-EFFECTS OF NITRIC-OXIDE INHIBITION IN EXPERIMENTAL COLITIS
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DOI：
10.1152/ajpgi.1995.268.4.g673
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发表时间：
1995-04-01
影响因子：
4.5
通讯作者：
BLENNERHASSETT, MG
中科院分区：
文献类型：
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作者：
HOGABOAM, CM;JACOBSON, K;BLENNERHASSETT, MG
我们探讨了一氧化氮在三硝基苯磺酸(TNB)结肠炎中的作用。每隔24 h灌胃N-G-硝基-L-精氨酸甲酯(L-NAME，30 mg/kg)、N-G-硝基-D-精氨酸甲酯(D-NAME)或水，测定大鼠摄食量、体重和血浆亚硝酸盐水平。第6天检测结肠一氧化氮合酶和髓过氧化物酶活性、组织学、肠肌生长、NADPH-黄递酶和肌间神经功能。在结肠炎的前72小时内，进食量和体重都减少了。在TNB术后第6天，检测到粘膜一氧化氮合酶增加了4倍，MPG增加了30倍，血浆亚硝酸盐增加了5倍。两个结肠肌层的平滑肌增生和肥大，肌间神经丛中有大量黄递酶阳性的巨噬细胞，肌间神经功能受到抑制。与D-NAME不同，口服L-NAME可使髓过氧化物酶活性降低90%，肠道肌肉增生减少90%。同样，血浆亚硝酸盐和结肠一氧化氮合酶也降低了70%。L-NAME可完全阻止巨噬细胞渗入肌肉。相反，它对厌食或肠平滑肌肥大没有影响，也不影响肌间神经递质的释放。这些结果证实了L-NAME对炎症结肠的选择性跨壁保护作用，提示一氧化氮是一种介质。
We investigated the involvement of nitric oxide in trinitrobenzenesulfonic acid (TNB) colitis. Every 24 h after TNB, rats were orally dosed with N-G-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg), N-G-nitro-D-arginine methyl ester (D-NAME), or water, and food intake, body weight, and plasma nitrite levels were measured. On day 6, colonic nitric oxide synthase and myeloperoxidase (MPG) activity, histology, intestinal muscle growth, NADPH-diaphorase, and myenteric nerve function were assessed. Food intake and body weight were reduced during the first 72 h of colitis. On day 6 post-TNB, a fourfold increase in mucosal nitric oxide synthase, a 30-fold increase in MPG, and a fivefold elevation in plasma nitrite were measured. Smooth muscle hyperplasia and hypertrophy in both colonic muscle layers, numerous diaphorase-positive macrophages in the myenteric plexus, and a suppression of myenteric nerve function were also observed. Unlike D-NAME, oral L-NAME reduced MPO and intestinal muscle hyperplasia by >90%. Likewise, plasma nitrite and colonic nitric oxide synthase were reduced by >70%. L-NAME completely prevented macrophage infiltration into the muscle. Conversely, it had no effect on anorexia or intestinal smooth muscle hypertrophy, nor did it affect suppressed myenteric nerve neurotransmitter release. These results demonstrate the selective transmural protective effects of L-NAME in the inflamed colon, implicating nitric oxide as a mediator.