In vitro and in vivo wound healing-promoting activities of β-lapachone
In vitro and in vivo wound healing-promoting activities of β-lapachone
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DOI：
10.1152/ajpcell.00266.2008
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发表时间：
2008-10-01
影响因子：
5.5
通讯作者：
Lu, Kuo-Shyan
中科院分区：
文献类型：
--
作者：
Kung, Hsiu-Ni;Yang, Mei-Jun;Lu, Kuo-Shyan
创面愈合受损是糖尿病患者的一个严重问题。伤口愈合是一个复杂的过程，需要多种细胞的协同作用，包括角质形成细胞、成纤维细胞、内皮细胞和巨噬细胞。β-拉帕酮是从罗汉果树(Tabebuia Avellanedae)树皮中提取的一种天然化合物，在不同的浓度和条件下具有抗肿瘤、抗炎和抗肿瘤作用，但其对伤口愈合的影响尚未被研究。本研究旨在探讨β-拉帕酮对创面愈合的影响及其机制。在本研究中，我们证明了低剂量的β-雷帕酮促进了几种细胞的增殖，促进了小鼠3T3成纤维细胞和人内皮细胞EAhy926细胞通过不同的MAPK信号通路迁移，并促进了体外擦伤愈合。在正常和糖尿病(db/db)小鼠(db/db)的穿孔伤口上应用含有或不含有β-拉帕酮的软膏，结果表明，在使用β-拉帕酮的动物中，愈合过程比仅使用赋形剂的动物要快。此外，β-拉帕酮还能诱导巨噬细胞释放有利于多种细胞生长的血管内皮生长因子和表皮生长因子。结果表明，β-拉帕酮可促进角质形成细胞、成纤维细胞和内皮细胞的增殖，促进成纤维细胞和内皮细胞的迁移，从而促进创面愈合。因此，我们认为β-拉帕酮可能具有治疗伤口愈合的潜力。
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.