Rafailidis Savas, Ballas Konstantinos, Psarras Kyriakos, Pavlidis Theodoros, Emoniotou Eleni, Papamichali Rodoula, Kalodimos Georges, Marakis Georges, Sakadamis Athanassios, Koukoulis Georges
Second Propedeutical Department of Surgery, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece.
J Gastroenterol. 2008;43(11):897-904. doi: 10.1007/s00535-008-2243-0. Epub 2008 Nov 18.
This study was conducted to investigate the effect of chronic bosentan administration on the development of esophageal varices in carbon tetrachloride-induced cirrhosis in rats.
For the development of liver cirrhosis and esophageal varices, 60 rats underwent ligation of the left adrenal vein, followed by phenobarbital and carbon tetrachloride administration. Two weeks after the beginning of carbon tetrachloride administration, rats were separated into two groups. In group I, comprising 30 rats, bosentan was continuously administered throughout the study, whereas in group II, also 30 rats, placebo instead of bosentan was continuously administered. Hemodynamic studies and morphometric analysis of the lower esophagus were performed after complete induction of cirrhosis. The total number of veins counted in the submucosa, the number of submucosal veins/mm(2) of submucosa, the total submucosal area occupied by vessels, the mean cross-sectional vessel area, the relative submucosal area (percentage) occupied by vessels, and the area of the single most-dilated submucosal vein were studied.
Bosentan induced a significant (P < 0.05) decrease in portal pressure, while morphometric analysis revealed a significant reduction (P < 0.05) of all parameters studied in bosentan-treated rats, except in the total and relative number of submucosal veins.
Bosentan administration seemed to significantly attenuate dilation of submucosal veins in the lower esophagus of cirrhotic rats. This effect was mainly attributed to a decrease in the portal pressure induced by chronic bosentan administration.
本研究旨在探讨长期给予波生坦对四氯化碳诱导的大鼠肝硬化食管静脉曲张发展的影响。
为诱导肝硬化和食管静脉曲张,60只大鼠接受左肾上腺静脉结扎,随后给予苯巴比妥和四氯化碳。在开始给予四氯化碳两周后,将大鼠分为两组。第一组30只大鼠,在整个研究过程中持续给予波生坦;第二组同样30只大鼠,持续给予安慰剂而非波生坦。在肝硬化完全诱导后,进行血流动力学研究和食管下段的形态计量分析。研究了黏膜下层计数的静脉总数、每平方毫米黏膜下层的黏膜下静脉数量、血管占据的黏膜下总面积、平均血管横截面积、血管占据的相对黏膜下面积(百分比)以及单个最扩张的黏膜下静脉面积。
波生坦使门静脉压力显著降低(P < 0.05),而形态计量分析显示,在接受波生坦治疗的大鼠中,除黏膜下静脉的总数和相对数量外,所有研究参数均显著降低(P < 0.05)。
给予波生坦似乎可显著减轻肝硬化大鼠食管下段黏膜下静脉的扩张。这种作用主要归因于长期给予波生坦引起的门静脉压力降低。