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胃食管反流病中的毒性胆汁酸:胃酸的影响

Toxic bile acids in gastro-oesophageal reflux disease: influence of gastric acidity.

作者信息

Nehra D, Howell P, Williams C P, Pye J K, Beynon J

机构信息

Singleton Hospital, Swansea, UK.

出版信息

Gut. 1999 May;44(5):598-602. doi: 10.1136/gut.44.5.598.

Abstract

BACKGROUND

Bile acid toxicity has been shown in the gastric, colonic, and hepatic tissues; the effect on oesophageal mucosa is less well known.

AIMS

To determine the spectrum of bile acids refluxing in patients with gastro-oesophageal reflux disease and its relation to oesophageal pH using a new technique of combined oesophageal aspiration and pH monitoring.

METHODS

Ten asymptomatic subjects and 30 patients with symptoms of gastro-oesophageal reflux disease (minimal mucosal injury, erosive oesophagitis (grade 2 or 3 Savary-Miller), Barrett's oesophagus/stricture; n=10 in each group) underwent 15 hour continuous oesophageal aspiration with simultaneous pH monitoring. Bile acid assay of the oesophageal samples was performed using modified high performance liquid chromatography.

RESULTS

The peak bile acid concentration and DeMeester acid scores were significantly higher in the patients with oesophagitis (median bile acid concentration 124 micromol/l; acid score 20.2) and Barrett's oesophagus/stricture (181 micromol/l; 43. 3) than patients with minimal injury (14 micromol/l; 12.5) or controls (0 micromol/l; 11.1). The predominant bile acids detected were cholic, taurocholic, and glycocholic acids but there was a significantly greater proportion of secondary bile acids, deoxycholic and taurodeoxycholic acids, in patients with erosive oesophagitis and Barrett's oesophagus/stricture. Although bile acid reflux episodes occurred at variable pH, a temporal relation existed between reflux of taurine conjugates and oesophageal acid exposure (r=0.58, p=0.009).

CONCLUSION

Toxic secondary bile acid fractions have been detected in patients with extensive mucosal damage. Mixed reflux is more harmful than acid reflux alone with possible toxic synergism existing between the taurine conjugates and acid.

摘要

背景

胆汁酸毒性已在胃、结肠和肝组织中得到证实;其对食管黏膜的影响尚鲜为人知。

目的

采用食管联合抽吸与pH监测新技术,确定胃食管反流病患者反流胆汁酸的种类及其与食管pH值的关系。

方法

10名无症状受试者和30例有胃食管反流病症状的患者(黏膜损伤轻微、糜烂性食管炎(Savary-Miller 2级或3级)、巴雷特食管/狭窄;每组10例)接受15小时的连续食管抽吸并同步进行pH监测。采用改良高效液相色谱法对食管样本进行胆汁酸检测。

结果

食管炎患者(胆汁酸浓度中位数124微摩尔/升;酸评分20.2)和巴雷特食管/狭窄患者(181微摩尔/升;43.3)的胆汁酸峰值浓度和DeMeester酸评分显著高于黏膜损伤轻微的患者(14微摩尔/升;12.5)或对照组(0微摩尔/升;11.1)。检测到的主要胆汁酸为胆酸、牛磺胆酸和甘胆酸,但在糜烂性食管炎和巴雷特食管/狭窄患者中,次级胆汁酸脱氧胆酸和牛磺脱氧胆酸的比例显著更高。尽管胆汁酸反流发作时pH值各不相同,但牛磺酸结合物反流与食管酸暴露之间存在时间关系(r = 0.58,p = 0.009)。

结论

在有广泛黏膜损伤的患者中检测到了有毒的次级胆汁酸组分。混合反流比单纯酸反流更有害,牛磺酸结合物与酸之间可能存在毒性协同作用。

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