Dexamethasone delays ulcer healing by inhibition of angiogenesis in rat stomachs
Dexamethasone delays ulcer healing by inhibition of angiogenesis in rat stomachs
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DOI：
10.1016/j.ejphar.2003.11.038
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发表时间：
2004-02-06
影响因子：
5
通讯作者：
Cho, CH
中科院分区：
文献类型：
--
作者：
Luo, JC;Shin, VY;Cho, CH
使用非致溃疡剂量的地塞米松，我们探讨了糖皮质激素对溃疡愈合的作用及其与胃粘膜血管生成因子的关系。我们对醋酸诱发的胃溃疡大鼠进行胃内注射地塞米松（0.1 或 0.2 mg/kg/天）。测定溃疡边缘黏膜前列腺素E-2水平以及碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）蛋白表达量。溃疡诱导显着增加了溃疡边缘bFGF、VEGF和前列腺素E-2的蛋白表达水平以及溃疡边缘和基底部的血管生成。非致溃疡剂量的地塞米松抑制溃疡边缘和溃疡基部的血管生成并延迟溃疡愈合。这些与前列腺素 E-2 水平和 VEGF 表达的显着降低有关，但与 bFGF 表达无关。补充前列腺素E-2减弱了地塞米松对VEGF表达的抑制作用，逆转了地塞米松对血管生成和溃疡愈合的不利影响，且不影响bFGF表达。我们得出的结论是，以非致溃疡剂量给予地塞米松可以减少血管生成并延迟乙酸诱导的溃疡愈合；这些作用至少部分是由于前列腺素 E-2 水平下降以及胃溃疡边缘 VEGF 下调所致。 (C) 2003 Elsevier B.V. 保留所有权利。
Using the non-ulcerogenic doses of dexamethasone, we explored the action of glucocorticoids on ulcer healing and its relationship with angiogenic factors in the gastric mucosa. We applied dexamethasone (0.1 or 0.2 mg/kg/day) intragastrically in rats with acetic acid-induced gastric ulcer. The mucosal prostaglandin E-2 level and protein expressions of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) at the ulcer margin were determined. Ulcer induction significantly increased protein expressions of bFGF, VEGF, and prostaglandin E-2 level at the ulcer margin together with angiogenesis at the ulcer margin and base. The non-ulcerogenic doses of dexamethasone inhibited angiogenesis at the ulcer margin and ulcer base and delayed ulcer healing. These were associated with a significant decrease of prostaglandin E-2 level and VEGF expression, but not the bFGF expression. Supplementation with prostaglandin E-2 attenuated the inhibitory action of dexamethasone on VEGF expression and reversed the adverse effects of dexamethasone on angiogenesis and ulcer healing, without influencing bFGF expression. We concluded that dexamethasone given at non-ulcerogenic doses could decrease angiogenesis and delay acetic acid-induced ulcer healing; these actions were at least, in part, due to depletion of prostaglandin E-2 level followed by down-regulation of VEGF at the ulcer margin of the stomach. (C) 2003 Elsevier B.V. All rights reserved.