Bulbena O, Culat J, Bravo M L
Department of Pharmacology, Laboratorios Viñas, S.A., Barcelona, Spain.
Inflammation. 1997 Oct;21(5):475-88. doi: 10.1023/a:1027355528929.
The present study was undertaken to evaluate the cytoprotective activity in the gastric mucosa of rats subjected to CCl4-induced liver injury. Response of gastric mucosa to absolute ethanol insult or acid (pylorus ligation) after CCl4 challenge was analyzed. Intraperitoneal administration of CCl4 increased plasma AST and ALT, but liver protein and glycogen levels were decreased; in addition, gastric acid secretion was significantly increased with respect to control animals (1541 +/- 266 vs. 629 +/- 25 mu eq H+; p < 0.001). Microscopical gastric erosions were observed in 3/10 animals after CCl4 challenge. Pylorus-ligated as well as CCl4-challenged rats developed increased susceptibility to gastric lesions, compared to control (lesion indices: 4.6 +/- 0.20 vs 2.8 +/- 0.13; p < 0.05), while showing increased resistance to absolute ethanol-induced gastric damage (30.4 +/- 11.2 vs 89.7 +/- 9.7 mm, p < 0.01). PGE2 levels in the gastric mucosa were not influenced by exposure to CCl4. Ultrastructural studies revealed the presence of continuous ethanol-resistant and apparently more adherent layer of mucus in CCl4-challenged animals. Morphological evaluation revealed an increase in Alcian blue-stained mucus. A dual condition of enhanced sensitivity to HCl with increased tolerance to ethanol was observed in gastric mucosa of CCl4-treated animals. These observations could be explained by the amount and/or composition of protective mucus layer in the gastric mucosa.
本研究旨在评估四氯化碳诱导肝损伤大鼠胃黏膜的细胞保护活性。分析了四氯化碳攻击后胃黏膜对无水乙醇损伤或酸(幽门结扎)的反应。腹腔注射四氯化碳可使血浆谷草转氨酶(AST)和谷丙转氨酶(ALT)升高,但肝脏蛋白质和糖原水平降低;此外,与对照动物相比,胃酸分泌显著增加(1541±266对629±25微当量H⁺;p<0.001)。四氯化碳攻击后,在10只动物中有3只观察到显微镜下的胃糜烂。与对照相比,幽门结扎以及四氯化碳攻击的大鼠对胃损伤的易感性增加(损伤指数:4.6±0.20对2.8±0.13;p<0.05),而对无水乙醇诱导的胃损伤的抵抗力增加(30.4±11.2对89.7±9.7毫米,p<0.01)。胃黏膜中的前列腺素E2(PGE2)水平不受四氯化碳暴露的影响。超微结构研究显示,在四氯化碳攻击的动物中存在连续的抗乙醇且明显更粘附的黏液层。形态学评估显示阿尔新蓝染色的黏液增加。在四氯化碳处理的动物胃黏膜中观察到对盐酸敏感性增强和对乙醇耐受性增加的双重情况。这些观察结果可以用胃黏膜中保护性黏液层的数量和/或组成来解释。