Department of General Surgery, Zonguldak Karaelmas University, Medical Faculty, 67600 Kozlu, Zonguldak, Turkey.
World J Gastroenterol. 2009 Oct 28;15(40):5091-6. doi: 10.3748/wjg.15.5091.
To investigate the gastroprotective effect of vardenafil against indomethacin-induced gastric damage.
Forty-eight female Wistar albino rats were randomly divided into 6 groups. Group 1 received saline only. Group 2 (indomethacin) received indomethacin. Rats in group 3 and 4 were pretreated with different doses of famotidine. Group 5 and 6 were pretreated with different doses of vardenafil. Rats in groups 3 to 6 received 25 mg/kg indomethacin 30 min after pretreatment. The animals were sacrificed 6 h later and their stomachs were opened. Gastric lesions were counted and measured. The stomach of each animal was divided in two parts for histopathological examinations and nitric oxide (NO) and malondialdehyde (MDA) assays, respectively.
There were no gastric mucosal lesion in the saline group but all rats in the indomethacin group had gastric mucosal ulcerations (ulcer count; 6.25 +/- 3.49, and mean ulcer area; 21.00 +/- 12.35). Ulcer counts were diminished with famotidine 5 mg/kg (4.12 +/- 2.47, P > 0.05), 20 mg/kg (2.37 +/- 4.43, P < 0.05), vardenafil 2 mg/kg (4.37 +/- 3.06), and vardenafil 10 mg/kg (1.25 +/- 1.38, P < 0.05) compared to the indomethacin group. Gastric mucosal lesion areas were diminished with famotidine 5 mg/kg (8.62 +/- 2.97, P < 0.001) , famotidine 20 mg/kg (0.94 +/- 2.06, P < 0.001), vardenafil 2 mg/kg (6.62 +/- 5.87, P < 0.001), and vardenafil 10 mg/kg (0.75 +/- 0.88, P < 0.001) compared to the indomethacin group. MDA levels were significantly higher in indomethacin group (28.48 +/- 14.51), compared to the famotidine 5 mg/kg (6,21 +/- 1.88, P < 0.05), famotidine 20 mg/kg (5.88 +/- 1.60. P < 0.05), vardenafil 2 mg/kg (15.87 +/- 3.93, P < 0.05), and vardenafil 10 mg/kg (10.97 +/- 4.50, P < 0.05). NO concentration in gastric tissues of the famotidine groups were significantly increased (P < 0.05), but the NO increases in the vardenafil groups were not statistically significant. Histopathology revealed diminished gastric damage for pretreatment groups compared to the indomethacin group (P < 0.05).
Vardenafil affords a significant dose-dependent protection against indomethacin induced gastric mucosal lesions in rats.
研究伐地那非对吲哚美辛诱导的胃损伤的胃保护作用。
将 48 只雌性 Wistar 白化大鼠随机分为 6 组。第 1 组仅接受生理盐水。第 2 组（吲哚美辛）接受吲哚美辛。第 3 组和第 4 组大鼠分别用不同剂量的法莫替丁预处理。第 5 组和第 6 组用不同剂量的伐地那非预处理。第 3 组至第 6 组大鼠在预处理后 30 分钟给予 25mg/kg 吲哚美辛。6 小时后处死动物，打开胃。计数胃损伤并测量。将每个动物的胃分为两部分，分别进行组织病理学检查和测定一氧化氮（NO）和丙二醛（MDA）。
生理盐水组胃黏膜无损伤，但吲哚美辛组所有大鼠均出现胃黏膜溃疡（溃疡数为 6.25 +/- 3.49，平均溃疡面积为 21.00 +/- 12.35）。与吲哚美辛组相比，法莫替丁 5mg/kg（4.12 +/- 2.47，P > 0.05）、20mg/kg（2.37 +/- 4.43，P < 0.05）、伐地那非 2mg/kg（4.37 +/- 3.06）和伐地那非 10mg/kg（1.25 +/- 1.38，P < 0.05）可减少溃疡数。与吲哚美辛组相比，法莫替丁 5mg/kg（8.62 +/- 2.97，P < 0.001）、法莫替丁 20mg/kg（0.94 +/- 2.06，P < 0.001）、伐地那非 2mg/kg（6.62 +/- 5.87，P < 0.001）和伐地那非 10mg/kg（0.75 +/- 0.88，P < 0.001）可减少胃黏膜损伤面积。与法莫替丁 5mg/kg（6，21 +/- 1.88，P < 0.05）、法莫替丁 20mg/kg（5.88 +/- 1.60，P < 0.05）、伐地那非 2mg/kg（15.87 +/- 3.93，P < 0.05）和伐地那非 10mg/kg（10.97 +/- 4.50，P < 0.05）相比，吲哚美辛组 MDA 水平显着升高。胃组织中 NO 浓度明显升高（P < 0.05），但伐地那非组的 NO 升高无统计学意义。组织病理学显示预处理组与吲哚美辛组相比胃损伤减轻（P < 0.05）。
伐地那非对吲哚美辛诱导的大鼠胃黏膜损伤具有显著的剂量依赖性保护作用。
