Kung Hsiu-Ni, Yang Mei-Jun, Chang Chi-Fen, Chau Yat-Pang, Lu Kuo-Shyan
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan .
Am J Physiol Cell Physiol. 2008 Oct;295(4):C931-43. doi: 10.1152/ajpcell.00266.2008. Epub 2008 Jul 23.
Impaired wound healing is a serious problem for diabetic patients. Wound healing is a complex process that requires the cooperation of many cell types, including keratinocytes, fibroblasts, endothelial cells, and macrophages. beta-Lapachone, a natural compound extracted from the bark of the lapacho tree (Tabebuia avellanedae), is well known for its antitumor, antiinflammatory, and antineoplastic effects at different concentrations and conditions, but its effects on wound healing have not been studied. The purpose of the present study was to investigate the effects of beta-lapachone on wound healing and its underlying mechanism. In the present study, we demonstrated that a low dose of beta-lapachone enhanced the proliferation in several cells, facilitated the migration of mouse 3T3 fibroblasts and human endothelial EAhy926 cells through different MAPK signaling pathways, and accelerated scrape-wound healing in vitro. Application of ointment with or without beta-lapachone to a punched wound in normal and diabetic (db/db) mice showed that the healing process was faster in beta-lapachone-treated animals than in those treated with vehicle only. In addition, beta-lapachone induced macrophages to release VEGF and EGF, which are beneficial for growth of many cells. Our results showed that beta-lapachone can increase cell proliferation, including keratinocytes, fibroblasts, and endothelial cells, and migration of fibroblasts and endothelial cells and thus accelerate wound healing. Therefore, we suggest that beta-lapachone may have potential for therapeutic use for wound healing.
伤口愈合受损对糖尿病患者来说是一个严重问题。伤口愈合是一个复杂的过程，需要多种细胞类型的协同作用，包括角质形成细胞、成纤维细胞、内皮细胞和巨噬细胞。β-拉帕醌是一种从拉帕乔树（Tabebuia avellanedae）树皮中提取的天然化合物，在不同浓度和条件下以其抗肿瘤、抗炎和抗瘤作用而闻名，但它对伤口愈合的影响尚未得到研究。本研究的目的是探讨β-拉帕醌对伤口愈合的影响及其潜在机制。在本研究中，我们证明低剂量的β-拉帕醌可增强几种细胞的增殖，通过不同的丝裂原活化蛋白激酶（MAPK）信号通路促进小鼠3T3成纤维细胞和人内皮EAhy926细胞的迁移，并在体外加速刮擦伤口愈合。在正常和糖尿病（db/db）小鼠的穿刺伤口上涂抹含或不含β-拉帕醌的软膏，结果显示，用β-拉帕醌治疗的动物的愈合过程比仅用赋形剂治疗的动物更快。此外，β-拉帕醌诱导巨噬细胞释放血管内皮生长因子（VEGF）和表皮生长因子（EGF），这对许多细胞的生长有益。我们的结果表明，β-拉帕醌可增加包括角质形成细胞和成纤维细胞及内皮细胞在内的细胞增殖，促进成纤维细胞和内皮细胞的迁移，从而加速伤口愈合。因此，我们认为β-拉帕醌可能具有用于伤口愈合治疗的潜力。
