Department of Pharmacology, Faculty of Medicine, El-Minia University, El-Minia, Egypt.
Nitric Oxide. 2012 Aug 15;27(2):117-22. doi: 10.1016/j.niox.2012.06.001. Epub 2012 Jun 8.
Nebivolol, a β(1)-adrenoceptor antagonist, exhibits vasodilatory and anti-oxidative properties that rendering it attractive candidate for protecting against gastric ulcer. The aim of this study therefore is to evaluate the protective effects of nebivolol against cold restraint stress (CRS)-induced gastric ulcer in rats. Rats were restrained, and maintained at 4°C for 3 h. Nebivolol (5 mg/kg, p.o.) was suspended in 0.5% aqueous solution of carboxymethyl cellulose and was administered 30 min before CRS. Nebivolol exhibited gastroprotective effects as evidenced by significant decreases in ulcer index as well as free and total acid output, and pepsin activity in gastric juice in addition to gastric mucosal malondialdehyde concentration, with concomitant increases in gastric juice pH and mucin concentration along with gastric mucosal reduced glutathione and nitric oxide (NO) concentrations compared with CRS rats. Moreover, immunohistochemical analysis demonstrated that nebivolol treatment markedly enhanced heme oxygenase-1 as well as cyclooxygenase-1 and cyclooxygenase-2 expressions. The protective effects of nebivolol were confirmed by gastric histopathological examination. Pretreatment with N(ω)-nitro-L-arginine, a NO synthase inhibitor, partly altered the protection afforded by nebivolol. In conclusion, nebivolol protected rats' gastric mucosa against CRS-induced gastric ulceration possibly through anti-oxidant activity, enhancement of gastric mucosal barrier and reduction in acid secretory parameters.
比索洛尔，一种β(1)-肾上腺素受体拮抗剂，具有血管扩张和抗氧化作用，使其成为预防胃溃疡的有吸引力的候选药物。因此，本研究旨在评估比索洛尔对大鼠冷束缚应激（CRS）诱导胃溃疡的保护作用。大鼠被束缚并保持在 4°C 下 3 小时。比索洛尔（5mg/kg，po）悬浮在 0.5%羧甲基纤维素水溶液中，并在 CRS 前 30 分钟给药。比索洛尔表现出胃保护作用，表现为溃疡指数以及游离和总酸分泌以及胃蛋白酶活性显著降低，此外，胃黏膜丙二醛浓度降低，胃液 pH 值和粘蛋白浓度升高，胃黏膜还原型谷胱甘肽和一氧化氮（NO）浓度升高，与 CRS 大鼠相比。此外，免疫组织化学分析表明，比索洛尔治疗显著增强血红素加氧酶-1以及环加氧酶-1 和环加氧酶-2 的表达。胃组织病理学检查证实了比索洛尔的保护作用。一氧化氮合酶抑制剂 N(ω)-硝基-L-精氨酸预处理部分改变了比索洛尔提供的保护作用。总之，比索洛尔通过抗氧化活性、增强胃黏膜屏障和减少胃酸分泌参数来保护大鼠胃黏膜免受 CRS 诱导的胃溃疡。
