Zijlstra F J, Srivastava E D, Rhodes M, van Dijk A P, Fogg F, Samson H J, Copeman M, Russell M A, Feyerabend C, Williams G T
Department of Gastroenterology, University Hospital of Wales, Cardiff, UK.
Gut. 1994 Feb;35(2):247-51. doi: 10.1136/gut.35.2.247.
Because ulcerative colitis is largely a disease of non-smokers and nicotine may have a beneficial effect on the disease, the effect of nicotine on rectal mucosa in rabbits was examined. Nicotine was given subcutaneously by an Alzet mini-pump in doses of 0.5, 1.25, and 2 mg/kg/day for 14 days to three groups of eight animals and compared with eight controls. Mean (SD) serum nicotine concentrations (ng/ml) were 3.5 (1.1), 8.8 (2.3), and 16.2 (5.2) respectively in the treated groups. The thickness of adherent mucus on rectal mucosa in controls (median 36 microns) was significantly reduced by low dose (22 microns, p = 0.0011), and increased by high dose nicotine (48 microns, p = 0.035). Incorporation of radioactive glucosamine into papain resistant glycoconjugates was unchanged, indicating that mucin synthesis was unaltered. Prostaglandins (PG) were reduced, in some cases significantly (6-keto PGF1 alpha, PGF2 alpha, and hydroxy-eicosatetraenoic acid), by nicotine, which showed an inverse dose dependence--with greatest inhibition in relation to the lowest dose. Nicotine, and possibly smoking, may affect colitis by an action on mucosal eicosanoids and on adherent surface mucus secretion in the rectum and large bowel.
由于溃疡性结肠炎主要是一种非吸烟者的疾病,且尼古丁可能对该疾病有有益影响,因此研究了尼古丁对兔直肠黏膜的作用。通过Alzet微型泵以0.5、1.25和2mg/kg/天的剂量对三组每组8只动物皮下注射尼古丁,持续14天,并与8只对照组动物进行比较。治疗组的平均(标准差)血清尼古丁浓度(ng/ml)分别为3.5(1.1)、8.8(2.3)和16.2(5.2)。对照组直肠黏膜上附着黏液的厚度(中位数36微米)在低剂量尼古丁作用下显著降低(22微米,p = 0.0011),而在高剂量尼古丁作用下增加(48微米,p = 0.035)。放射性葡糖胺掺入抗木瓜蛋白酶糖缀合物的情况未发生变化,表明黏蛋白合成未改变。尼古丁可降低前列腺素(PG)水平,在某些情况下显著降低(6-酮基前列腺素F1α、前列腺素F2α和羟基二十碳四烯酸),呈剂量依赖性反比关系——最低剂量时抑制作用最大。尼古丁以及可能的吸烟行为,可能通过作用于黏膜类花生酸以及直肠和大肠中附着的表面黏液分泌来影响结肠炎。