Ohrui T, Yamaya M, Suzuki T, Sekizawa K, Funayama T, Sekine H, Sasaki H
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
Chest. 1997 Feb;111(2):454-9. doi: 10.1378/chest.111.2.454.
The respiratory aspiration of the stomach contents causes severe lung damage called aspiration pneumonia. The present study was undertaken to elucidate whether mucosal exposure of gastric juice causes hyperpermeability of the human airway epithelium and to determine the mechanisms responsible for gastric juice-induced airway epithelial damage.
Gastric juice was collected from 46 normal adults via gastroscope and samples were analyzed for pH, osmolarity, and concentration of pepsin and trypsin. Tracheal surface epithelial cells were obtained from 16 autopsies, cultured onto porous filters, and mounted in the Ussing chamber. Electrical conductance (G) was measured before and after exposure of cells to gastric juice or Krebs-Henseleit solution with pH at 1.8, 2.8, 4.0, or 7.4 in the presence or absence of pepsin. D-[3H] mannitol flux study across the epithelial layer and histologic observations using an inverted microscope were also performed after exposure of cells to gastric juice.
Exposure of cultured human tracheal epithelium to gastric juice caused increases in G in a time- and pH-dependent fashion. A pepsin inhibitor (pepstatin A) inhibited gastric juice-induced increases in G at a pH of 2.8, and the addition of pepsin augmented increases in G induced by the Krebs-Henseleit solution at a pH of 1.8 and 2.8. Lowering the osmolarity of the solution to levels similar to gastric juice also potentiated increases in G induced by acid and pepsin. Gastric juice caused increases in D-[3H] mannitol flux across the epithelial layer bidirectionally, and microscopic observation revealed separation of the intercellular space and cell detachment from culture vessels after exposure of cells to gastric juice.
Gastric juice causes hyperpermeability across human airway epithelium probably through the additive effects of gastric acid, pepsin activity, and lower osmolarity.
胃内容物的呼吸性误吸会导致严重的肺损伤，称为误吸性肺炎。本研究旨在阐明胃液的黏膜暴露是否会导致人气道上皮细胞的通透性增加，并确定导致胃液诱导气道上皮损伤的机制。
通过胃镜从46名正常成年人中收集胃液，并对样本进行pH值、渗透压以及胃蛋白酶和胰蛋白酶浓度的分析。从16例尸检中获取气管表面上皮细胞，将其培养在多孔滤膜上，并安装在尤斯灌流小室中。在存在或不存在胃蛋白酶的情况下，将细胞暴露于pH值为1.8、2.8、4.0或7.4的胃液或克雷布斯-亨泽莱特溶液之前和之后，测量跨上皮层的电阻抗（G）。在细胞暴露于胃液后，还进行了跨上皮层的D-[3H]甘露醇通量研究以及使用倒置显微镜的组织学观察。
培养的人气管上皮细胞暴露于胃液后，G以时间和pH值依赖性方式增加。胃蛋白酶抑制剂（胃蛋白酶抑制剂A）在pH值为2.8时抑制胃液诱导的G增加，并且添加胃蛋白酶会增强克雷布斯-亨泽莱特溶液在pH值为1.8和2.8时诱导的G增加。将溶液的渗透压降低至与胃液相似的水平也会增强酸和胃蛋白酶诱导的G增加。胃液导致跨上皮层的D-[3H]甘露醇通量双向增加，显微镜观察显示细胞暴露于胃液后细胞间空间分离以及细胞从培养容器中脱离。
胃液可能通过胃酸、胃蛋白酶活性和较低渗透压的叠加作用导致人气道上皮细胞通透性增加。
