Pharmacology Dept, Alexandria University, Egypt.
Biochem Pharmacol. 2010 Jun 1;79(11):1634-9. doi: 10.1016/j.bcp.2010.02.001. Epub 2010 Feb 6.
The aim of the present study was to assess the effect of drugs that increase gastric vascular endothelial growth factor (VEGF) and suppress gastric tumor necrosis factor-alpha (TNF-alpha) in gastric ulcer healing in streptozotocin-induced diabetic rats. Sixty male albino rats were made diabetic by intraperitoneal (i.p.) streptozotocin injection and ten rats were injected i.p. by a single dose of saline. Six weeks following streptozotocin or saline injection, gastric ulcers were induced by serosal application of acetic acid. Three days after acetic acid application, rats were divided into: group I (non-diabetic control), group II (streptozotocin-injected), groups III-VII (streptozotocin-injected rats treated with insulin, insulin and pentoxifylline, insulin and simvastatin, pentoxifylline as well as simvastatin, respectively, for 7 days following acetic acid application. The use of insulin, combinations of insulin and pentoxifylline or simvastatin resulted in a significant decrease in gastric ulcer area, significant increase in epithelial regeneration assessed histologically, significant increase in gastric VEGF concentration, and gastric von Willebrand factor (vWF) as well as significant decrease in gastric TNF-alpha. A significant difference in gastric ulcer area as well as in gastric TNF-alpha, VEGF and vWF levels could be observed between rats that received combinations of insulin and pentoxifylline or simvastatin compared to rats that received either drug alone. Our results suggest the feasibility of a novel treatment strategy, namely pentoxifylline and simvastatin, for patients in whom impairment of ulcer healing constitutes a secondary complication of diabetes mellitus.
本研究旨在评估增加胃血管内皮生长因子（VEGF）和抑制胃肿瘤坏死因子-α（TNF-α）的药物对链脲佐菌素诱导的糖尿病大鼠胃溃疡愈合的影响。60 只雄性白化大鼠经腹腔（i.p.）链脲佐菌素注射制成糖尿病大鼠，10 只大鼠单次腹腔注射生理盐水。链脲佐菌素或生理盐水注射 6 周后，通过浆膜应用醋酸诱导胃溃疡。醋酸应用 3 天后，大鼠分为：第 I 组（非糖尿病对照组）、第 II 组（链脲佐菌素注射组）、第 III-VII 组（链脲佐菌素注射大鼠分别用胰岛素、胰岛素和己酮可可碱、胰岛素和辛伐他汀、己酮可可碱和辛伐他汀治疗 7 天）。胰岛素、胰岛素和己酮可可碱或辛伐他汀的联合使用可显著减少胃溃疡面积，组织学评估的上皮再生显著增加，胃 VEGF 浓度和胃血管性血友病因子（vWF）显著增加，胃 TNF-α显著减少。与单独使用任一药物的大鼠相比，联合使用胰岛素和己酮可可碱或辛伐他汀的大鼠的胃溃疡面积以及胃 TNF-α、VEGF 和 vWF 水平有显著差异。我们的结果表明，联合使用己酮可可碱和辛伐他汀可能是一种新的治疗策略，用于那些溃疡愈合受损是糖尿病继发并发症的患者。
