Konturek S J, Brzozowski T
J Physiol Pharmacol. 1991 Jun;42(2):107-33.
Gastric mucosal integrity depends upon the balance between "aggressive" factors and "defensive" mechanisms. The formation of mucosal lesions results from the disruption of defense lines, including the breaking of unstirred mucus layer, the reduction of surface hydrophobicity, extensive exfoliation of surface epithelium, penetration of offending agents deeply into the mucosa and damage to the microvessels. The release of proinflammatory and vasoactive mediators such as leukotrienes (LT), thromboxanes, platelet activating factor (PAF), endothelins and others has been thought to be involved in the pathomechanism of mucosal injury, especially damage to the microvascular endothelium, increased vascular permeability, reduction in mucosal blood flow, vascular stasis, tissue ischemia and glandular cell necrosis. This paper reviews the mechanisms and possible pathogenetic implication of two related compounds, LT and PAF in acute mucosal injury by topical irritants such as ethanol, aspirin, bile salts and by stress. LT and PAF arise from similar membrane phospholipids and may regulate the biosynthesis of one another in the damaged mucosa. Although pharmacological studies have clearly demonstrated the noxious effects of cysteinyl LT and PAF on the mucosa, especially when exposed to topical irritants, recent publications have challenged the primary role of these mediators in the pathogenesis of mucosal lesions and ulcerations because the treatment with agents that selectively antagonize their biosynthesis or the receptor sites at the target cells did not always interrupt the chain of events leading to mucosal injury. The role of these mediators in the mucosal repair processes has been little studied but both cysteinyl LT and PAF seem to delay the restitution and healing of the mucosa. Further studies are necessary to clarify to what extent the biosynthesis of LT and PAF and the pharmacological inhibition of their action on the target tissues is related to noxious, protective and reparative events in the mucosa exposed to mild irritants and ulcerogens.
胃黏膜完整性取决于“攻击”因素与“防御”机制之间的平衡。黏膜损伤的形成是由于防御防线的破坏，包括静止黏液层的破裂、表面疏水性的降低、表面上皮细胞的广泛脱落、有害因子深入黏膜以及微血管的损伤。促炎和血管活性介质如白三烯（LT）、血栓素、血小板活化因子（PAF）、内皮素等的释放被认为参与了黏膜损伤的发病机制，尤其是对微血管内皮的损伤、血管通透性增加、黏膜血流减少、血管淤滞、组织缺血和腺细胞坏死。本文综述了两种相关化合物LT和PAF在乙醇、阿司匹林、胆盐等局部刺激物及应激所致急性黏膜损伤中的机制及可能的发病学意义。LT和PAF源自相似的膜磷脂，且在受损黏膜中可能相互调节生物合成。尽管药理学研究已明确证实半胱氨酰LT和PAF对黏膜有有害作用，尤其是在暴露于局部刺激物时，但最近的出版物对这些介质在黏膜损伤和溃疡发病机制中的主要作用提出了质疑，因为用选择性拮抗其生物合成或靶细胞受体位点的药物进行治疗并不总能中断导致黏膜损伤的一系列事件。这些介质在黏膜修复过程中的作用研究较少，但半胱氨酰LT和PAF似乎都会延迟黏膜的恢复和愈合。有必要进一步研究以阐明LT和PAF的生物合成以及对其在靶组织上作用的药理学抑制在多大程度上与暴露于轻度刺激物和致溃疡物质的黏膜中的有害、保护和修复事件相关。
