Proteolytic activity in wound fluids and tissues derived from chronic venous leg ulcers

Proteolytic activity in wound fluids and tissues derived from chronic venous leg ulcers
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DOI:
10.1111/j.1524-475x.2009.00547.x
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发表时间:
2009-11-01
影响因子:
2.9
通讯作者:
Gould, Lisa J.
Gould, Lisa J.
中科院分区:
医学3区
文献类型:
--
作者:
Moor, Andrea N.;Vachon, David J.;Gould, Lisa J.

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下肢静脉溃疡影响大约1%的一般人群和3.6%的65岁以上人群。本文所述研究的目标是通过开发基于对静脉溃疡伤口环境的全面了解的伤口护理替代方案来缩短愈合时间。伤口液体和组织活检样本中的蛋白水解和炎症成分的特点是在受试者与记录长期静脉溃疡,已显示出对标准治疗的阻力。所有伤口均显示多种微生物定植,且大于106 CFU/g。髓过氧化物酶,白细胞浸润的措施,也显着升高,在这些伤口。酶谱法显示在伤口液中存在基质金属蛋白酶原(MMP)-2和MMP-9原,在组织活检中存在程度较低。使用免疫捕获活性测定,我们揭示了七倍过量的MMP-9在伤口液相比,组织,73%的活化形式。相比之下,MMP-8总蛋白水平几乎相等的伤口液和活检。纤连蛋白,细胞外基质的关键成分,被证明是降解的伤口液和活检样品。最后,一种新型的伤口敷料,以中和这种敌对的伤口环境的几个成分的潜力。
Venous leg ulcers affect approximately 1% of the general population and 3.6% of those over the age of 65. The goal of the research described herein is to shorten the time to healing by developing wound care alternatives that are based on a comprehensive understanding of the venous ulcer wound environment. The proteolytic and inflammatory components in wound fluids and tissue biopsy samples were characterized in subjects with documented long-standing venous ulcers that had showed resistance to standard therapy. All wounds showed polymicrobial colonization with greater than 106 CFU/g. Myeloperoxidase, a measure of leukocyte infiltration, was also markedly elevated in these wounds. Zymography revealed the presence of both pro-matrix metalloproteinase (MMP)-2 and pro-MMP-9 in wound fluids and to a lesser extent in tissue biopsies. Using an immunocapture activity assay we reveal a sevenfold excess of MMP-9 in wound fluid as compared to tissue, with 73% in the activated form. In contrast, MMP-8 total protein levels were nearly equal in wound fluids and biopsies. Fibronectin, a critical component of the extracellular matrix, was shown to be degraded in both wound fluids and biopsy samples. Finally, the potential of a novel wound dressing to neutralize several constituents of this hostile wound environment is shown.