Department of Integrative Biology and Physiology, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
Curr Opin Gastroenterol. 2011 Oct;27(6):543-8. doi: 10.1097/MOG.0b013e32834b3fcb.
We have highlighted the recent findings relating to gastroduodenal mucosal defense, including elements that may contribute to the failure of defense systems and factors that enhance mucosal healing, focusing on findings that elucidate new pathophysiological mechanisms.
Bicarbonate secretion is mediated by multiple types of prostaglandin E synthases, including membrane-bound prostaglandin E synthase-1. Mucins, growth factors, and trefoil factors are involved in accelerating gastric injury healing through epithelial reconstruction. A combination of NSAIDs and bile induce greater damage on the mucosa than if the two agents were acting alone. Proton pump inhibitors defend the mucosa from injury by promoting cellular restitution as well as inhibiting gastric acid secretion and reactive oxygen species (ROS) damage. Roxatidine, a novel H2 receptor antagonist, acts through a mechanism that involves nitric oxide. Melatonin enhances angiogenesis through the upregulation of plasma levels of gastrin and matrix metalloproteinase expression. The mucosal protective drug polaprezinc exhibits ROS-quenching activities. Lipopolysaccharides induce oxidative stress mediated by p38 mitogen-activated protein kinase (p38 MAPK). Aging weakens gastroduodenal mucosal defense mechanisms.
There is a wide array of pathways leading to gastroduodenal mucosal injury in addition to protective defense mechanisms that counteract them to maintain homeostasis. Increased understanding of these systems may help identify novel molecular targets for the prevention and treatment of mucosal injury.
我们强调了与胃十二指肠黏膜防御相关的最新发现，包括可能导致防御系统失效的因素和增强黏膜愈合的因素，重点介绍了阐明新病理生理机制的发现。
碳酸氢盐分泌由多种类型的前列腺素 E 合酶介导，包括膜结合前列腺素 E 合酶-1。黏蛋白、生长因子和三叶因子通过上皮重建加速胃损伤愈合。非甾体抗炎药和胆汁的联合作用比两种药物单独作用对黏膜造成更大的损伤。质子泵抑制剂通过促进细胞修复以及抑制胃酸分泌和活性氧（ROS）损伤来保护黏膜免受损伤。新型 H2 受体拮抗剂罗沙替丁通过涉及一氧化氮的机制发挥作用。褪黑素通过上调胃泌素和基质金属蛋白酶表达来促进血管生成。黏膜保护药物聚普瑞锌具有 ROS 清除活性。脂多糖通过 p38 丝裂原活化蛋白激酶（p38 MAPK）诱导氧化应激。衰老使胃十二指肠黏膜防御机制减弱。
除了对抗维持内稳态的防御机制外，还有多种导致胃十二指肠黏膜损伤的途径。对这些系统的深入了解可能有助于确定预防和治疗黏膜损伤的新分子靶点。
