THE GASTRODUODENAL MUCUS BARRIER AND ITS ROLE IN PROTECTION AGAINST LUMINAL PEPSINS - THE EFFECT OF 16,16-DIMETHYL PROSTAGLANDIN-E(2), CARBOPOL-POLYACRYLATE, SUCRALFATE AND BISMUTH SUBSALICYLATE
THE GASTRODUODENAL MUCUS BARRIER AND ITS ROLE IN PROTECTION AGAINST LUMINAL PEPSINS - THE EFFECT OF 16,16-DIMETHYL PROSTAGLANDIN-E(2), CARBOPOL-POLYACRYLATE, SUCRALFATE AND BISMUTH SUBSALICYLATE
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DOI：
10.1111/j.1440-1746.1994.tb01303.x
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发表时间：
1994-01-01
影响因子：
4.1
通讯作者：
ALLEN, A
中科院分区：
文献类型：
--
作者：
COPEMAN, M;MATUZ, J;ALLEN, A
粘液和碳酸氢盐分泌物被广泛认为是一种重要的前上皮保护屏障，可以防止胃粘膜被酸和胃蛋白酶自身消化。几项独立研究的证据表明，胃十二指肠粘膜表面粘附有一层连续的弹性粘弹性粘液凝胶。人体粘附胃粘液层的中位厚度为180 μ m，范围为50-450 μ m。上皮碳酸氢盐分泌物渗透粘液凝胶的未搅拌基质，中和管腔酸并在凝胶内建立pH梯度。在十二指肠中，有证据支持粘液碳酸氢盐屏障作为对抗酸侵袭的主要保护机制。粘附的粘液凝胶通过充当胃蛋白酶的有效“渗透性”屏障，保护下面敏感的粘膜免受消化。然而，胃蛋白酶在其腔表面缓慢地消化粘液凝胶以产生可溶性降解粘蛋白。在大鼠体内胃损伤模型中，过量胃蛋白酶迅速破坏胃粘液屏障，超过新的粘液分泌，导致粘液屏障破裂，在上皮中形成小点状溃疡，伴有粘膜出血。粘液促分泌素16，16二甲基前列腺素E（2）酸和粘液粘附性卡波姆-聚丙烯酸酯都通过增强粘液屏障的保护性能来充分保护粘膜免受胃蛋白酶损伤。硫糖铝和碱式水杨酸铋对胃蛋白酶损伤的保护作用部分有效，但这种保护作用主要是在粘膜水平介导的。在消化性溃疡疾病中，胃液中的粘液溶解（粘液降解）活性增加，这与粘蛋白聚合结构受损和粘液屏障较弱有关。这些研究的证据支持（i）粘附的粘液层是胃中抵抗胃蛋白酶侵袭的主要保护屏障;（ii）在单独的酸无效的情况下，胃蛋白酶本身是一种粘膜损伤剂;（iii）胃蛋白酶是一种胃蛋白酶。和（iii）粘液屏障对胃蛋白酶攻击的抵抗力降低可能是消化性溃疡病的病因学因素。
Mucus and bicarbonate secretions have been widely implicated as an important pre-epithelial protective barrier against autodigestion of the gastric mucosa by acid and pepsin. Evidence from several independent studies shows there is a continuous layer of resilient viscoelastic mucus gel adherent to the surface of the gastroduodenal mucosa. The median thickness of the adherent gastric mucus layer in humans is 180 mu m, range 50-450 mu m. The epithelial bicarbonate secretion permeates the unstirred matrix of mucus gel neutralizing luminal acid and establishing a pH gradient within the gel. In the duodenum, evidence supports the mucus bicarbonate barrier as a major protective mechanism against acid aggression.The adherent mucus gel, by acting as an effective 'permeability' barrier to pepsin, protects the underlying sensitive mucosa from digestion. However, pepsin slowly digests mucus gel at its luminal surface to produce soluble degraded mucin. In a rat gastric damage model in vivo, pepsin in excess digests the gastric mucus barrier sufficiently rapidly to outweigh new mucus secretion and lead to breaching of the mucus barrier with the formation of small punctate ulcers in the epithelium accompanied by mucosal haemorrhage. The mucus secretagogue 16,16 dimethyl prostaglandin E(2) acid the muco-adhesive carbopol-polyacrylate both fully protected the mucosa against pepsin damage by enhancing the protective properties of the mucus barrier. Sucralfate and bismuth subsalicylate were partially effective in protection against pepsin damage but this protection was mainly mediated at the level of the mucosa. In peptic ulcer disease, there is increased mucolytic (mucus degrading) activity in gastric juice and this is associated with an impaired mucin polymeric structure and a weaker mucus barrier. This enhanced mucolysis can be explained by increased levels of pepsin 1 secretion in peptic ulcer disease.Evidence from these studies supports (i) the adherent mucus layer as a major protective barrier against pepsin aggression in the stomach; (ii) that pepsin is a mucosal damaging agent per se under conditions where acid alone is ineffective; and (iii) decreased resistance of the mucus barrier to pepsin aggression could be a factor in the aetiology of peptic ulcer disease.