Department and Institute of Life Science, Fu-Jen Catholic University, Taipei, Taiwan.
Eur J Pharm Sci. 2012 Dec 18;47(5):875-83. doi: 10.1016/j.ejps.2012.08.018. Epub 2012 Sep 14.
Impairment in diabetic wound healing constitutes an enormous biomedical burden. The receptor for advanced glycation end-products (RAGE) expression in the diabetic cutaneous wound may play a key role. However, the relationship between RAGE expression and topical application of anti-oxidant agents with gold nanoparticles (AuNP) in cutaneous diabetic wounds remains unclear. We tested the 3-5 nm AuNP, epigallocatechin gallate (EGCG), and α-lipoic acid (ALA) could change the RAGE expression and be helpful in diabetic wound. The mixture of AuNP+EGCG+ALA (AuEA) significantly attenuated the AGE-induced RAGE protein expression in fibroblasts (Hs68). Topical EGCG+ALA (EA) and AuEA application accelerated wound healing on diabetic mouse skin and decreased the RAGE expression. Vascular endothelial growth factor but not angiopoietin-1 significantly increased after EA or AuEA treatment for 7 days. Angiopoietin-2 significantly decreased at day 7 in AuEA group. Furthermore, immunoblotting of diabetic wound tissue showed significant decrease of CD68 expression from day 3 to day 7. The results suggest that combination of AuNP, EGCG, and ALA significantly accelerated diabetic cutaneous wound healing through angiogenesis regulation and anti-inflammatory effects. Blockade of RAGE by anti-oxidant agents and nanoparticles may restore effective wound healing in diabetic ulcer.
糖尿病创面愈合受损构成了巨大的医学负担。晚期糖基化终产物（RAGE）在糖尿病皮肤创面的表达可能起着关键作用。然而，RAGE 表达与在皮肤糖尿病创面局部应用抗氧化剂与金纳米粒子（AuNP）之间的关系尚不清楚。我们测试了 3-5nm 的 AuNP、表没食子儿茶素没食子酸酯（EGCG）和α-硫辛酸（ALA）可以改变 RAGE 表达，并有助于糖尿病伤口愈合。AuNP+EGCG+ALA（AuEA）混合物显著减弱了成纤维细胞（Hs68）中 AGE 诱导的 RAGE 蛋白表达。局部 EGCG+ALA（EA）和 AuEA 应用加速了糖尿病小鼠皮肤的伤口愈合，并降低了 RAGE 表达。血管内皮生长因子而非血管生成素-1 在 EA 或 AuEA 治疗 7 天后显著增加。在 AuEA 组中，血管生成素-2 在第 7 天显著下降。此外，糖尿病创面组织的免疫印迹显示，从第 3 天到第 7 天，CD68 的表达显著下降。结果表明，AuNP、EGCG 和 ALA 的联合应用通过血管生成调节和抗炎作用显著加速了糖尿病皮肤创面的愈合。抗氧化剂和纳米粒子对 RAGE 的阻断可能恢复糖尿病溃疡的有效愈合。
