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一氧化氮介导尼古丁对溃疡性结肠炎的治疗作用。

Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis.

作者信息

Green J T, Richardson C, Marshall R W, Rhodes J, McKirdy H C, Thomas G A, Williams G T

机构信息

Department of Gastroenterology, University Hospital of Wales, Cardiff, UK.

出版信息

Aliment Pharmacol Ther. 2000 Nov;14(11):1429-34. doi: 10.1046/j.1365-2036.2000.00847.x.

DOI:10.1046/j.1365-2036.2000.00847.x
PMID:11069313
Abstract

BACKGROUND

Ulcerative colitis is a condition of nonsmokers in which nicotine is of therapeutic benefit.

AIMS

To examine the in vitro effect of nicotine on colonic smooth muscle activity and the role of nitric oxide (NO) as a mediator.

METHODS

Nicotine, 1-10 microM, was administered to strips of circular muscle from the distal sigmoid colon of 9 patients with active ulcerative colitis and 18 with colorectal cancer. The effect of electrical field stimulation (EFS) was examined before nicotine was added. Finally L-NAME, a NO synthetase inhibitor, was added before nicotine was administered again.

RESULTS

Muscle strips developed similar spontaneous resting tone. In response to EFS, ulcerative colitis tissue developed lower tensions than the controls. Nicotine significantly reduced the resting tone and peak tension after EFS, with a greater effect in controls. With L-NAME, peak tensions were increased more in ulcerative colitis than controls, and nicotine produced a much smaller reduction.

CONCLUSIONS

Nicotine reduces circular muscle activity, predominantly through the release of nitric oxide-this appears to be 'up-regulated' in active ulcerative colitis. These findings may explain some of the therapeutic benefit from nicotine (and smoking) in ulcerative colitis and may account for the colonic motor dysfunction in active disease.

摘要

背景

溃疡性结肠炎是一种在非吸烟者中出现的疾病,尼古丁对其具有治疗作用。

目的

研究尼古丁对结肠平滑肌活动的体外作用以及一氧化氮(NO)作为介质的作用。

方法

将1-10微摩尔的尼古丁施用于9例活动性溃疡性结肠炎患者和18例结直肠癌患者的乙状结肠远端环形肌条。在添加尼古丁之前检测电场刺激(EFS)的效果。最后,在再次施用尼古丁之前添加NO合酶抑制剂L-NAME。

结果

肌条呈现出相似的自发静息张力。对EFS的反应中,溃疡性结肠炎组织产生的张力低于对照组。尼古丁显著降低了静息张力和EFS后的峰值张力,对对照组的作用更大。使用L-NAME后,溃疡性结肠炎的峰值张力比对照组增加得更多,而尼古丁产生的降低作用则小得多。

结论

尼古丁主要通过一氧化氮的释放降低环形肌活动——这在活动性溃疡性结肠炎中似乎是“上调”的。这些发现可能解释了尼古丁(和吸烟)在溃疡性结肠炎中的一些治疗益处,并可能解释活动性疾病中的结肠运动功能障碍。

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