Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.
J Dent Res. 2014 Apr;93(4):388-93. doi: 10.1177/0022034514523785. Epub 2014 Feb 19.
The blocking of advanced glycation end-products (AGE) has been shown to reduce diabetic complications and control periodontitis. This study investigated the pattern of palatal wound-healing after graft harvesting under the administration of aminoguanidine (AG), an AGE inhibitor, or N-phenacylthiazolium bromide (PTB), a glycated cross-link breaker. Full-thickness palatal excisional wounds (5.0 x 1.5 mm(2)) were created in 72 Sprague-Dawley rats. The rats received daily intraperitoneal injections of normal saline (control), AG, or PTB and were euthanized after 4 to 28 days. The wound-healing pattern was assessed by histology, histochemistry for collagen matrix deposition, immunohistochemistry for AGE and the AGE receptor (RAGE), and the expression of RAGE, as well as inflammation- and recovery-associated genes. In the first 14 days following AG or PTB treatments, wound closure, re-epithelialization, and collagen matrix deposition were accelerated, whereas AGE deposition, RAGE-positive cells, and inflammation were reduced. RAGE and tumor necrosis factor-alpha were significantly down-regulated at day 7, and heme oxygenase-1 was persistently down-regulated until day 14. The levels of vascular endothelial growth factor, periostin, type I collagen, and fibronectin were all increased at day 14. In conclusion, anti-AGE agents appeared to facilitate palatal wound-healing by reducing AGE-associated inflammation and promoting the recovery process.
阻断晚期糖基化终产物 (AGE) 已被证明可以减少糖尿病并发症并控制牙周炎。本研究调查了氨基胍 (AG)，一种 AGE 抑制剂，或 N-苯甲酰硫代唑啉溴化物 (PTB)，一种糖化交联破坏剂给药后腭部创面愈合的模式。在 72 只 Sprague-Dawley 大鼠中创建了全厚腭切开创面（5.0 x 1.5 mm(2)）。大鼠每天接受腹膜内注射生理盐水（对照）、AG 或 PTB，并在 4 至 28 天后处死。通过组织学、胶原基质沉积的组织化学、AGE 和 AGE 受体 (RAGE) 的免疫组织化学以及 RAGE 的表达以及炎症和恢复相关基因来评估伤口愈合模式。在 AG 或 PTB 治疗后的前 14 天，伤口闭合、再上皮化和胶原基质沉积加速，而 AGE 沉积、RAGE 阳性细胞和炎症减少。RAGE 和肿瘤坏死因子-α 在第 7 天显著下调，血红素加氧酶-1 一直下调至第 14 天。血管内皮生长因子、骨膜蛋白、I 型胶原和纤维连接蛋白的水平在第 14 天均升高。总之，抗 AGE 剂似乎通过减少 AGE 相关炎症和促进恢复过程来促进腭部创面愈合。
