Nishizaki Y, Guth P H, Sternini C, Kaunitz J D
Medical Service, West Los Angeles Veterans Affairs Medical Center, California, USA.
Am J Physiol. 1996 Jan;270(1 Pt 1):G71-8. doi: 10.1152/ajpgi.1996.270.1.G71.
Liver cirrhosis impairs gastric mucosal resistance to luminal acid in humans and in animal models. Because we have previously shown that pentagastrin enhances defensive as well as aggressive factors implicated in mucosal injury, we examined the hypothesis that the pentagastrin-mediated enhancement of mucosal defense mechanisms may be impaired in cirrhotic rats. Increased acid backdiffusion and susceptibility to gross mucosal injury, associated with an elimination of the hyperemic response to gastric barrier disruption, was observed in cirrhotic rats. In in vivo microscopic studies in anesthetized rats, cirrhosis had no effect on pentagastrin-associated enhancement of mucus gel thickness or baseline gastric mucosal blood flow, although baseline mucus gel thickness was decreased. Cirrhosis did, however, abolish the luminal acid-related hyperemic response to pentagastrin, which was associated with impaired intracellular pH homeostasis during acid superfusion. Cirrhosis did not alter submucosal calcitonin gene-related peptide immunoreactive nerves. We conclude that acid backdiffusion and pentagastrin-associated hyperemic responses are important mucosal defensive factors that are specifically impaired by cirrhosis.
在人类和动物模型中，肝硬化会损害胃黏膜对腔内酸的抵抗力。因为我们之前已经表明，五肽胃泌素会增强与黏膜损伤相关的防御和攻击因素，所以我们检验了这样一个假设：在肝硬化大鼠中，五肽胃泌素介导的黏膜防御机制增强可能受损。在肝硬化大鼠中观察到酸反向扩散增加以及对严重黏膜损伤的易感性增加，同时消除了对胃屏障破坏的充血反应。在对麻醉大鼠进行的体内显微镜研究中，肝硬化对五肽胃泌素相关的黏液凝胶厚度增加或基线胃黏膜血流量没有影响，尽管基线黏液凝胶厚度有所降低。然而，肝硬化确实消除了腔内酸相关的对五肽胃泌素的充血反应，这与酸灌注期间细胞内pH稳态受损有关。肝硬化并没有改变黏膜下降钙素基因相关肽免疫反应性神经。我们得出结论，酸反向扩散和五肽胃泌素相关的充血反应是重要的黏膜防御因素，而肝硬化会使其特别受损。
