Modlin I M, Basson M D, Adrian T E, Sussman J
Dept. of Surgery, Yale University School of Medicine, New Haven, CT 06510.
Scand J Gastroenterol. 1990 Sep;25(9):865-75. doi: 10.3109/00365529008997606.
Despite blockade and neutralization of gastric acid, acute gastric lesions cause substantial morbidity and mortality in critically ill patients. Pepsinogen release in response to noxious stimuli such as hypoxia and endotoxin might contribute to mucosal damage. Guinea pig fundic mucosa was mounted in Ussing chambers. Acid secretion, pepsinogen release, potential difference (PD), and resistance were monitored. Gassing with room air or nitrogen diminished acid secretion and PD but increased pepsinogen release 9.7- and 15.5-fold, respectively (both p less than 0.001). Similarly, endotoxin (0.01 and 0.1 units/ml) dose-dependently inhibited acid secretion and PD but increased pepsinogen release 3.3- and 6.1-fold (both p less than 0.05). Endotoxic and air-gassed tissues were edematous with scattered cellular damage by light and transmission electron microscopy; nitrogen-exposed membranes appeared necrotic. Pepsin release may therefore have resulted from cell damage rather than exocytosis. Intragastric peptic activity in critically ill H2-receptor-blocked patients (n = 20) was 5490 +/- 1701 U/ml. The gastric juice of H2-blocked convalescing surgical patients (n = 20) contained 315 +/- 101 U/ml (p less than 0.0001). Occult blood correlated with intragastric peptic activity (r = 0.59, p less than 0.0001) but not with gastric pH (r = 0.04, p = 0.6). These data suggest that the complex of pathophysiologic abnormalities common in critical illness causes substantial pepsin release. Efflux of this potent mucolytic barrier breaker may damage gastric mucosa in severely stressed patients.
尽管胃酸被阻断和中和，但急性胃损伤在重症患者中仍会导致相当高的发病率和死亡率。胃蛋白酶原对缺氧和内毒素等有害刺激的释放可能导致黏膜损伤。将豚鼠胃底黏膜置于尤斯灌流小室中。监测胃酸分泌、胃蛋白酶原释放、电位差（PD）和电阻。用室内空气或氮气通气可减少胃酸分泌和PD，但分别使胃蛋白酶原释放增加9.7倍和15.5倍（两者p均小于0.001）。同样，内毒素（0.01和0.1单位/毫升）剂量依赖性地抑制胃酸分泌和PD，但使胃蛋白酶原释放增加3.3倍和6.1倍（两者p均小于0.05）。通过光学显微镜和透射电子显微镜观察，内毒素处理和通气组织出现水肿，伴有散在的细胞损伤；暴露于氮气的组织出现坏死。因此，胃蛋白酶的释放可能是细胞损伤而非胞吐作用所致。重症H2受体阻断患者（n = 20）的胃内消化活性为5490±1701 U/ml。康复期手术H2受体阻断患者（n = 20）的胃液中含有315±101 U/ml（p小于0.0001）。潜血与胃内消化活性相关（r = 0.59，p小于0.0001），但与胃pH值无关（r = 0.04，p = 0.6）。这些数据表明，危重病中常见的病理生理异常复合体可导致大量胃蛋白酶释放。这种强大的黏液溶解屏障破坏剂的外流可能会损伤重症患者的胃黏膜。
