牛磺酸对大鼠胃中一氯胺诱导的致溃疡反应及溃疡愈合受损的影响。

Effect of taurine on ulcerogenic response and impaired ulcer healing induced by monochloramine in rat stomachs.

作者信息

Kato S, Umeda M, Takeeda M, Kanatsu K, Takeuchi K

机构信息

Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, Japan.

出版信息

Aliment Pharmacol Ther. 2002 Apr;16 Suppl 2:35-43. doi: 10.1046/j.1365-2036.16.s2.12.x.

DOI:10.1046/j.1365-2036.16.s2.12.x

PMID:11966522

Abstract

BACKGROUND

It is well known that neutrophil-derived hypochlorous acid interacts with ammonia (NH4OH) to generate monochloramine (NH2Cl) and that NH2Cl irritates the gastric mucosa and impairs ulcer healing.

AIM

To examine the effect of taurine, a hypochlorous acid scavenger, on the mucosal ulcerogenic and the impaired healing response induced by NH2Cl in rat stomachs, in comparison with those of methionine and glycine.

METHODS AND RESULTS

Under anaesthesia, oral administration of NH2Cl (120 mmol/L) produced severe lesions in male Sprague-Dawley rat stomachs. Taurine (10-100 mg/kg) given p.o. 30 min prior to NH2Cl dose-dependently prevented these lesions in response to NH2Cl. This action was mimicked by methionine (3-30 mg/kg) but not by glycine (10-100 mg/kg). Under urethane anaesthesia, mucosal exposure to NH4OH (120 mmol/L) caused a marked reduction of potential difference (PD) in the ex vivo chambered stomachs after induction of ischaemia, resulting in severe lesions. These ulcerogenic and PD responses by NH4OH plus ischaemia were also mitigated by taurine and methionine, but not glycine, applied to the chamber 20 min before the onset of NH4OH plus ischaemia. Moreover, oral administration of 100% ethanol produced severe haemorrhagic lesions in rat stomachs, all of which rapidly healed within 7 days after lesion induction. Daily administration of NH2Cl (20 mmol/L) significantly delayed the healing of these lesions, but recovery of this impaired healing response was obtained by concurrent administration of taurine. Both taurine and methionine showed a potent scavenging effect against NH2Cl in vitro.

CONCLUSIONS

(1) NH2Cl generated either exogenously or endogenously damages the gastric mucosa and impairs the healing response; (2) taurine exerts a prophylactic effect against the deleterious effects of NH2Cl, mainly due to its scavenging action against NH2Cl; and (3) this effect of taurine may be useful for treatment of gastritis associated with Helicobacter pylori infection.

摘要

背景

众所周知，中性粒细胞衍生的次氯酸与氨（NH₄OH）相互作用生成一氯胺（NH₂Cl），且NH₂Cl会刺激胃黏膜并损害溃疡愈合。

目的

与蛋氨酸和甘氨酸相比，研究次氯酸清除剂牛磺酸对大鼠胃中由NH₂Cl诱导的黏膜溃疡形成及愈合反应受损的影响。

方法与结果

在麻醉状态下，口服NH₂Cl（120 mmol/L）会在雄性Sprague-Dawley大鼠胃中产生严重损伤。在给予NH₂Cl前30分钟口服牛磺酸（10 - 100 mg/kg）可剂量依赖性地预防这些由NH₂Cl引起的损伤。蛋氨酸（3 - 30 mg/kg）可模拟此作用，而甘氨酸（10 - 100 mg/kg）则不能。在氨基甲酸乙酯麻醉下，在离体有腔胃中诱导缺血后，黏膜暴露于NH₄OH（120 mmol/L）会导致电位差（PD）显著降低，从而产生严重损伤。在NH₄OH加缺血开始前20分钟将牛磺酸和蛋氨酸应用于腔室，可减轻由NH₄OH加缺血引起的这些溃疡形成和PD反应，但甘氨酸无效。此外，口服100%乙醇会在大鼠胃中产生严重的出血性损伤，所有这些损伤在损伤诱导后7天内迅速愈合。每日给予NH₂Cl（20 mmol/L）会显著延迟这些损伤的愈合，但同时给予牛磺酸可恢复这种受损的愈合反应。牛磺酸和蛋氨酸在体外均对NH₂Cl显示出强大的清除作用。