Masuda E, Kawano S, Nagano K, Tsuji S, Takei Y, Hayashi N, Tsujii M, Oshita M, Michida T, Kobayashi I
First Department of Medicine, Osaka University Medical School, Japan.
Am J Physiol. 1993 Sep;265(3 Pt 1):G474-81. doi: 10.1152/ajpgi.1993.265.3.G474.
The major objective of this study was to elucidate the role of endogenous endothelin (ET)-1, a potent vasoconstrictor peptide, in the pathogenesis of ethanol (EtOH)-induced gastric mucosal injury. Two series of experiments were performed in anesthetized rats. First, we examined the time course of relationships among changes in ET-1 concentrations in gastric mucosal and portal plasma, gastric mucosal hemodynamics, and mucosal damage produced by EtOH. Intragastric EtOH stimulated release of endogenous ET-1 in gastric mucosal tissue. Plasma ET-1 concentrations in the portal vein also increased after intragastric EtOH administration. ET-1 concentrations in gastric mucosal tissue and portal plasma increased significantly before gastric mucosal hemorrhagic damage occurred. Moreover, 30 min after EtOH administration there were significant correlations between gastric mucosal ET-1 concentrations and both area of gastric hemorrhagic damage as well as concentration of EtOH administered intragastrically. After intragastric EtOH administration, increase in gastric mucosal hemoglobin concentration and decrease in gastric mucosal hemoglobin oxygen saturation, estimated using reflectance spectrophotometry, occurred within 2.5 min and continued throughout the experiments. The time course of microcirculatory changes correlated closely with increases in gastric mucosal ET-1 and portal plasma ET-1 concentrations after intragastric EtOH administration. Gastric microcirculatory disturbances induced by EtOH were associated with significant decreases in gastric mucosal ATP content. Second, we examined whether pretreatment with anti-ET-1 antibody protected against EtOH-induced mucosal injury by improving mucosal microcirculation. Pretreatment with anti-ET-1 antibody microscopically and macroscopically reduced gastric mucosal hemorrhagic damage induced by EtOH and significantly reduced EtOH-induced gastric microcirculatory disturbances and decreases in gastric mucosal ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究的主要目的是阐明内源性内皮素（ET）-1（一种强力血管收缩肽）在乙醇（EtOH）诱导的胃黏膜损伤发病机制中的作用。在麻醉大鼠身上进行了两组实验。首先，我们研究了胃黏膜和门静脉血浆中ET-1浓度变化、胃黏膜血流动力学以及EtOH所致黏膜损伤之间关系的时间进程。胃内给予EtOH刺激胃黏膜组织释放内源性ET-1。胃内给予EtOH后门静脉血浆ET-1浓度也升高。在胃黏膜出血性损伤发生前，胃黏膜组织和门静脉血浆中的ET-1浓度显著升高。此外，给予EtOH 30分钟后，胃黏膜ET-1浓度与胃出血损伤面积以及胃内给予的EtOH浓度之间存在显著相关性。胃内给予EtOH后，使用反射分光光度法估计，胃黏膜血红蛋白浓度在2.5分钟内升高，胃黏膜血红蛋白氧饱和度降低，并在整个实验过程中持续存在。胃内给予EtOH后微循环变化的时间进程与胃黏膜ET-1和门静脉血浆ET-1浓度的升高密切相关。EtOH诱导的胃微循环障碍与胃黏膜ATP含量显著降低有关。其次，我们研究了用抗ET-1抗体预处理是否通过改善黏膜微循环来预防EtOH诱导的黏膜损伤。用抗ET-1抗体预处理在显微镜和宏观上均减少了EtOH诱导的胃黏膜出血性损伤，并显著减轻了EtOH诱导的胃微循环障碍和胃黏膜ATP的降低。（摘要截断于250字）
