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一种聚丙烯酸酯高吸水性聚合物对慢性伤口中基质金属蛋白酶活性的抑制作用

The inhibition of matrix metalloproteinase activity in chronic wounds by a polyacrylate superabsorber.

作者信息

Eming Sabine, Smola Hans, Hartmann Berenike, Malchau Gebhart, Wegner Ronny, Krieg Thomas, Smola-Hess Sigrun

机构信息

Department of Dermatology, University of Cologne, Kerpener Strasse 62, 50924 Cologne, Germany.

出版信息

Biomaterials. 2008 Jul;29(19):2932-40. doi: 10.1016/j.biomaterials.2008.03.029. Epub 2008 Apr 9.

Abstract

Excessive matrix metalloproteinase (MMP) levels have been observed in wound fluid of impaired healing wounds. This is thought to interfere with granulation tissue formation as newly formed extracellular matrix and cytokines are degraded and the wound becomes deadlocked, unable to progress to the next healing stages. In the cleansing phase, associated with high MMP activity levels, hydroactive wound dressings containing polyacrylate superabsorber particles are particularly effective. We tested whether these particles can block MMP activity in wound fluid obtained from chronic venous leg ulcers. Polyacrylate superabsorber particles inhibited MMP activity by more than 87% in a fluorogenic peptide substrate assay. Further analysis revealed two underlying molecular mechanisms. First, experiments showed direct binding of MMPs to the particles. Secondly, polyacrylate superabsorber particles can bind Ca2+ and Zn2+ ions competing with MMPs for divalent ions required for enzymatic activity. Furthermore, we provide the first evidence in vivo that MMPs bind effectively to polyacrylate superabsorber particles within the hostile environment of chronic wounds. We conclude that polyacrylate superabsorber particles can rescue the highly proteolytic microenvironment of non-healing wounds from MMP activity so that more conductive conditions allow healing to proceed.

摘要

在愈合受损伤口的伤口渗出液中已观察到基质金属蛋白酶(MMP)水平过高。据认为,这会干扰肉芽组织的形成,因为新形成的细胞外基质和细胞因子会被降解,伤口会陷入僵局,无法进入下一个愈合阶段。在与高MMP活性水平相关的清创阶段,含有聚丙烯酸酯超吸收颗粒的水活性伤口敷料特别有效。我们测试了这些颗粒是否能阻断从慢性下肢静脉溃疡获得的伤口渗出液中的MMP活性。在荧光肽底物测定中,聚丙烯酸酯超吸收颗粒抑制MMP活性超过87%。进一步分析揭示了两种潜在的分子机制。首先,实验表明MMP与颗粒直接结合。其次,聚丙烯酸酯超吸收颗粒可以结合Ca2+和Zn2+离子,与MMP竞争酶活性所需的二价离子。此外,我们首次在体内证明,在慢性伤口的恶劣环境中,MMP能有效地与聚丙烯酸酯超吸收颗粒结合。我们得出结论,聚丙烯酸酯超吸收颗粒可以使不愈合伤口的高蛋白水解微环境免受MMP活性的影响,从而使更有利于愈合的条件得以实现。

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