一氧化氮、内皮素及氧自由基对大鼠酒精性胃损害的作用研究

目的研究大鼠酒精性胃损害中,一氧化氮(NO)、内皮素(ET)和氧自由基的作用,以及NO对ET-1、丙二醛(MDA)水平的影响.方法以酒精给大鼠灌胃制备急性胃粘膜损害模型,实验分为五组,应用L-NAME或/和L-Arg依不同分组行尾静脉注射.取门脉血测定NO、ET-1和MDA水平,并取出胃进行形态学观察.结果酒精灌胃后,大鼠门脉血NO含量降低,ET-1和MDA量升高,粘膜损伤加重.L-NAME组NO进一步减少,ET-1和MDA更加升高,粘膜损伤明显加重.L-Arg与L-NAME合用后NO、ET-1及MDA水平均有不同程度恢复,粘膜损伤亦减轻.NO与ET-1及MDA水平呈负相关.结论在酒精性胃损害中,ET-1与氧自由基生成增加,起损害作用,内源性NO可调节ET-1的生成,清除氧自由基而发挥保护作用.

Role of nitric oxide, endothelin and oxygen free radicals in ethanol-induced gastric mucosal injury in rats

Aim To study the role of endogenous nitic oxide (NO), endothelin (ET) and oxygen free radicals in the ethanol-induced gastric mucosal injury and to observe the influence of NO on the levels of ET-1 and malondialdehyde (MDA). Methods The model of acute gastric mucosal injury in rat was induced by intragastric ethanol instillation. Thirty rats were divided into five groups. L-NAME or L-arginine (L-arg) with L-NAME was given intravenously in different groups. Portal blood samples were collected to measure the levels of NO, ET-1 and MDA. The area of gross gastric mucosal hemorrhagic damage and the histologic score of mucosal damage were assessed. Results After intragastric administration of ethanol, NO contents in the portal vein were decreased; the levels of ET-1 and MDA were increased; the area of gross gastric mucosal hemorrhagic damage and the histological scores became higher. In L-NAME group, NO contents were further reduced; the levels of ET-1 and MDA were further elevated; the gastric mucosal damage was markedly aggravated. In the group pretreated with L-arg and L-NAME, the levels of NO, ET-1 and MDA were recovered in varying degrees, while the mucosal injury was alleviated. NO content was negatively correlated with ET-1 level and MDA content. Conclusion In the acute gastric mucosal injury, the increased production of ET-1 and oxygen free radicals may exacerbate the mucosal damage. NO can regulate the production of ET-1 and scavenge oxygen free radicals, thus NO has protective function against the acute gastric mucosal injury.