慢性尼古丁给药对三硝基苯磺酸诱导的结肠炎的影响。

Effect of chronic nicotine administration on trinitrobenzene sulphonic acid-induced colitis.

作者信息

Eliakim R, Karmeli F, Rachmilewitz D, Cohen P, Fich A

机构信息

Department of Medicine, Hadassah University Hospital on Mount Scopus, Jerusalem, Israel.

出版信息

Eur J Gastroenterol Hepatol. 1998 Dec;10(12):1013-9.

PMID:9895047

Abstract

BACKGROUND

Smoking, probably due to nicotine, has a bivalent effect on inflammatory bowel disease, ameliorating disease activity in ulcerative colitis and with a deleterious effect on Crohn's disease. The effect of nicotine patches in ulcerative colitis is controversial.

AIM

To investigate the effect of chronic nicotine use in a rat model of colitis.

METHODS

Colitis was induced in Sprague-Dawley rats by rectal administration of 30 mg trinitrobenzene sulphonic acid (TNBS) in 50% ethanol. Nicotine was dissolved in drinking water (2.5, 12.5, 25 and 250 microg/ml), with rats drinking ad libitum. Nicotine administration started 10 days prior to damage induction and had no effect on weight gain or daily food intake of rats. Rats were sacrificed 1 and 5 days after TNBS administration, their colons resected, rinsed, weighed, damage assessed macroscopically (mm2) and microscopically and tissue processed for myeloperoxidase (MPO) and nitric oxide synthase (NOS) activities, leukotriene B4 (LTB4), prostaglandin E2 (PGE2) generation and interleukin-1 (IL-1) serum levels.

RESULTS

Nicotine, by itself, caused no damage to the colon. Nicotine had a dose-dependent bivalent effect on colitis, significantly reducing macroscopic damage from 983 +/- 10 mm2 on TNBS alone to 429 +/- 118 mm2 on TNBS plus 12.5 microg/ml of nicotine, and escalating to 1086 +/- 262 mm2 on 250 microg/ml of nicotine. Segmental weight declined significantly (from 2.4 +/- 0.2 to 1.65 +/- 0.20 g/10 cm), on 12.5 microg/ml nicotine, as did MPO activity (from 3.2 +/- 0.4 to 0.7 +/- 0.1 units/g). All these parameters returned to the levels of TNBS alone when the dose of nicotine was increased to 250 microg/ml. Nicotine had no effect on NOS activity, PGE2 generation and serum IL-1 levels, but increased LTB4 generation.

CONCLUSIONS

Nicotine has a dose-dependent bivalent effect on TNBS-induced colitis which is not due to reduction in IL-1 serum levels or PGE2 generation, and is not NOS-mediated.

摘要

背景

吸烟，可能是由于尼古丁，对炎症性肠病具有双重作用，可改善溃疡性结肠炎的疾病活动，但对克罗恩病有有害影响。尼古丁贴片在溃疡性结肠炎中的作用存在争议。

目的

研究慢性使用尼古丁在大鼠结肠炎模型中的作用。

方法

通过在50%乙醇中直肠给予30mg三硝基苯磺酸（TNBS）诱导斯普拉格-道利大鼠发生结肠炎。将尼古丁溶解于饮用水中（2.5、12.5、25和250μg/ml），大鼠自由饮水。在损伤诱导前10天开始给予尼古丁，且对大鼠体重增加或每日食物摄入量无影响。在给予TNBS后1天和5天处死大鼠，切除其结肠，冲洗、称重，宏观（mm²）和微观评估损伤情况，并对组织进行髓过氧化物酶（MPO）和一氧化氮合酶（NOS）活性、白三烯B4（LTB4）、前列腺素E2（PGE2）生成及白细胞介素-1（IL-1）血清水平检测。

结果

尼古丁本身对结肠无损伤。尼古丁对结肠炎具有剂量依赖性双重作用，显著降低宏观损伤，仅给予TNBS时为983±10mm²，给予TNBS加12.5μg/ml尼古丁时降至429±118mm²，而给予250μg/ml尼古丁时则升至1086±262mm²。给予12.5μg/ml尼古丁时，节段重量显著下降（从2.4±0.2降至1.65±0.20g/10cm），MPO活性也显著下降（从3.2±0.4降至0.7±0.1单位/g）。当尼古丁剂量增加至250μg/ml时，所有这些参数均恢复至仅给予TNBS时的水平。尼古丁对NOS活性、PGE2生成及血清IL-1水平无影响，但增加LTB4生成。