Hernández-Muñoz R, Montiel-Ruíz C, Vázquez-Martínez O
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México.
Lab Invest. 2000 Aug;80(8):1161-9. doi: 10.1038/labinvest.3780124.
The oxygen free radicals-induced lipid peroxidation (LP) has been implicated in the pathogenesis of acute ethanol-induced gastric mucosal lesions. However, the role of LP in the generation of chronic gastric mucosal injury is unknown. We have developed a model of chronic mucosal injury induced by continuous ethanol ingestion for 5 days and characterized by marked alterations in plasma membranes from gastric mucosa. Therefore, LP was evaluated in this experimental model. Indicators of peroxidative activity, mucosal glutathione content, thymidine kinase activity (an index of cell proliferation), and histamine H2-receptor (H2R) binding constants were quantified in animals undergoing gastric mucosal damage. The effect of famotidine, a H2R antagonist that readily ameliorates the chronic mucosal injury, was also tested. Increased free radicals and LP levels were detected during gastritis; however, a second, higher peak of LP was noted in mucosal plasma membranes after ethanol withdrawal (recovery period). This further increase of LP coincided with active cell proliferation, decreased mucosal glutathione levels, and diminished specific cimetidine binding by H2R. Administration of famotidine accelerated the mucosal proliferative process, inducing the second lipoperoxidative episode sooner, and preserved the content of glutathione. In addition, LP correlated directly with cell proliferation and inversely with mucosal membrane cimetidine binding. In conclusion, LP seems to be involved in chronic ethanol-induced gastric mucosal injury. However, a further enhancement of plasma membrane LP occurred, associated with increased DNA synthesis and diminished cimetidine binding by membrane H2R. Therefore, increased LP could also participate in the compensatory mucosal proliferation initiated after ethanol withdrawal.
氧自由基诱导的脂质过氧化（LP）被认为与急性乙醇诱导的胃黏膜损伤的发病机制有关。然而，LP在慢性胃黏膜损伤发生过程中的作用尚不清楚。我们建立了一个连续5天摄入乙醇诱导慢性黏膜损伤的模型，其特征是胃黏膜质膜有明显改变。因此，在这个实验模型中对LP进行了评估。对经历胃黏膜损伤的动物，定量检测了过氧化活性指标、黏膜谷胱甘肽含量、胸苷激酶活性（细胞增殖指标）以及组胺H2受体（H2R）结合常数。还测试了法莫替丁（一种能有效改善慢性黏膜损伤的H2R拮抗剂）的作用。在胃炎期间检测到自由基和LP水平升高；然而，在乙醇戒断后（恢复期），黏膜质膜中LP出现了第二个更高的峰值。LP的这种进一步升高与活跃的细胞增殖、黏膜谷胱甘肽水平降低以及H2R对西咪替丁的特异性结合减少同时发生。给予法莫替丁加速了黏膜增殖过程，更早地诱导了第二次脂质过氧化事件，并保留了谷胱甘肽的含量。此外，LP与细胞增殖直接相关，与黏膜膜西咪替丁结合呈负相关。总之，LP似乎参与了慢性乙醇诱导的胃黏膜损伤。然而，质膜LP进一步增强，这与DNA合成增加和膜H2R对西咪替丁结合减少有关。因此，LP增加也可能参与了乙醇戒断后启动的代偿性黏膜增殖。
