Lillemoe K D, Johnson L F, Harmon J W
Surgery. 1985 Jun;97(6):662-7.
Pepsin and trypsin cause erosive, hemorrhagic lesions in our rabbit model of experimental esophagitis. Since the gastroduodenal contents of patients with reflux esophagitis may also contain bile salts, we used our model to determine the effect that a bile salt, taurodeoxycholate (TDC), would have on the esophageal mucosa when combined with either pepsin in an acid perfusate (pH 2) or trypsin in an alkaline perfusate (pH 7.5). Indexes of esophageal injury included gross appearance of the mucosa, microscopic examination, and mucosal barrier integrity as determined by permeability to hydrogen ion. We found that when 5 mM TDC was combined with pepsin (0.3 mg/ml), the gross and microscopic changes of esophagitis, as well as net hydrogen ion flux, were diminished when compared with those observed with pepsin exposure alone. When increasing concentrations of TDC (2 to 10 mM) were added to pepsin, the morphologic degree of injury as well as hydrogen ion flux decreased in a dose-dependent manner. In contrast, when 5 mM TDC was combined with trypsin (1000 U/ml) in the alkaline perfusate, the gross and microscopic changes of esophagitis and the net of hydrogen ion flux were increased when compared with either bile salt or trypsin alone. These effects were also dose dependent. These data demonstrate that bile salts present in the gastroduodenal contents of patients with reflux esophagitis have the capacity to modulate the effects of pepsin and trypsin on the esophageal mucosa.
在我们的实验性食管炎兔模型中，胃蛋白酶和胰蛋白酶会导致糜烂性、出血性病变。由于反流性食管炎患者的胃十二指肠内容物中可能也含有胆汁盐，我们利用该模型来确定胆汁盐牛磺脱氧胆酸盐（TDC）在与酸性灌流液（pH 2）中的胃蛋白酶或碱性灌流液（pH 7.5）中的胰蛋白酶联合使用时，对食管黏膜会产生何种影响。食管损伤指标包括黏膜的大体外观、显微镜检查以及通过氢离子渗透性确定的黏膜屏障完整性。我们发现，当5 mM TDC与胃蛋白酶（0.3 mg/ml）联合使用时，与单独暴露于胃蛋白酶相比，食管炎的大体和显微镜下变化以及氢离子净通量均有所减轻。当向胃蛋白酶中添加浓度不断增加的TDC（2至10 mM）时，损伤的形态学程度以及氢离子通量呈剂量依赖性降低。相比之下，当在碱性灌流液中5 mM TDC与胰蛋白酶（1000 U/ml）联合使用时，与单独使用胆汁盐或胰蛋白酶相比，食管炎的大体和显微镜下变化以及氢离子净通量均增加。这些效应也是剂量依赖性的。这些数据表明，反流性食管炎患者胃十二指肠内容物中存在的胆汁盐有能力调节胃蛋白酶和胰蛋白酶对食管黏膜的作用。
