葡萄籽原花青素提取物对尿激酶型纤溶酶原激活物和纤溶酶原激活物抑制剂-1 的下调作用。

Downregulation of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 by grape seed proanthocyanidin extract.

机构信息

Department of Applied Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

出版信息

Phytomedicine. 2010 Jan;17(1):42-6. doi: 10.1016/j.phymed.2009.06.010. Epub 2009 Jul 28.

DOI:10.1016/j.phymed.2009.06.010

PMID:19640694

Abstract

Urokinase plasminogen activator (uPA) system, comprising of uPA, its receptor uPAR and inhibitor, type 1 plasminogen activator inhibitor (PAI-1), plays a vital role in various biological processes involving extracellular proteolysis, fibrinolysis, cell migration and proliferation. The timely occurence of these processes are essential for normal wound healing. This study examines the regulation of uPA and PAI-1 by a natural polyphenol-rich compound, grape seed extract (GSE). GSE is reported to have beneficial effects in promoting wound healing. Fibroblast cells exposed to different doses of GSE for 18hours were processed for further studies such as ELISA, RT-PCR, western blotting, fibrinolytic assay, cell surface plasmin activity assay and in vitro wound healing assay. GSE treatment caused a significant downregulation of uPA and PAI-1 expression, both at the RNA and protein levels. ELISA also revealed a dose-dependent decrease in uPA and PAI-1 activities. Functional significance of the downregulation was evident in decreased fibrinolytic activity, concomittant with decreased cell-surface plasmin activity. In vitro wound healing studies showed that GSE also retarded the migration of cells towards the wounded region.

摘要

尿激酶纤溶酶原激活物（uPA）系统，包括 uPA、其受体 uPAR 和抑制剂 1 型纤溶酶原激活物抑制剂（PAI-1），在涉及细胞外蛋白水解、纤维蛋白溶解、细胞迁移和增殖的各种生物学过程中发挥着重要作用。这些过程的及时发生对于正常的伤口愈合至关重要。本研究探讨了天然多酚丰富的化合物葡萄籽提取物（GSE）对 uPA 和 PAI-1 的调节作用。据报道，GSE 对促进伤口愈合有有益的影响。将成纤维细胞暴露于不同剂量的 GSE 18 小时，然后进行进一步的研究，如 ELISA、RT-PCR、western blot、纤维蛋白溶解测定、细胞表面纤溶酶活性测定和体外伤口愈合测定。GSE 处理导致 uPA 和 PAI-1 的表达显著下调，无论是在 RNA 还是蛋白质水平。ELISA 还显示 uPA 和 PAI-1 活性呈剂量依赖性下降。下调的功能意义在于纤维蛋白溶解活性降低，同时细胞表面纤溶酶活性降低。体外伤口愈合研究表明，GSE 还会延缓细胞向受伤区域的迁移。