Maniscalco Rosanna, Mangano Giorgina, de Joannon Alessandra Capezzone, Vergassola Matteo, Zucchi Sara, Mannello Ferdinando, Ragni Lorella
Unit of Clinical Biochemistry, Section of Biochemistry and Biotechnology, Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Scientific Consultant, ToxHub S.r.l. Albano Laziale, 00073 Rome, Italy.
J Clin Med. 2023 Apr 28;12(9):3189. doi: 10.3390/jcm12093189.
In chronic wounds, high concentrations of matrix metalloproteinases (MMPs) can cause excessive proteolysis and slow wound healing. Consequently, restoring a proper MMP balance can help reduce the risk of a chronic wound. An antiseptic solution containing 0.05% sodium hypochlorite (Amukine Med 0.05%, Angelini S.p.A.; hereafter termed NaClO solution) is available on the market. The NaClO solution was proven effective and safe in managing infected skin wounds. To further characterize its activity, this study evaluated the in vitro activity of the NaClO solution on the monocyte release of MMPs.
Human monocytic THP-1 (ATCC TIB-202™) cell lines were differentiated into macrophages and treated with different concentrations of NaClO (from 0.05% to 5 × 10%). In addition, the THP-1 cell line was stimulated with wound fluid (WF) from patients with active venous leg ulcers in the inflammatory phase. The effect of NaClO (0.025-0.0062%) was also evaluated on healthy human peripheral blood serum samples. The effects of treatments on the gelatinolytic activity of MMP-9 were evaluated by gelatin zymography. The effects on MMPs release were evaluated through the Pro™ Human MMP 9-plex Assay. An exploratory scratch wound healing assay was also performed.
The NaClO solution reduced the gelatinolytic activity of MMP-9 and its activated form. The downregulation of MMP-9 gelatinolytic activity was also observed in peripheral blood serum. The MMPs profile showed a reduction in MMP-1 release ( < 0.05) and a slight reduction of the release of MMP-9 and MMP-12 after the treatment with LPS and the NaClO solution. A slight improvement in wound healing was observed after macrophage activation and treatment with the NaClO solution.
The results obtained suggest a possible ability of the NaClO solution to modulate the proteolytic pathways in the wound microenvironment, further characterizing its activity and use in clinical practice during wound care.
在慢性伤口中,高浓度的基质金属蛋白酶(MMPs)可导致过度的蛋白水解并延缓伤口愈合。因此,恢复适当的MMP平衡有助于降低慢性伤口的风险。市场上有一种含有0.05%次氯酸钠的防腐溶液(Amukine Med 0.05%,安琪利尼制药公司;以下简称次氯酸钠溶液)。次氯酸钠溶液在处理感染性皮肤伤口方面已被证明是有效且安全的。为了进一步表征其活性,本研究评估了次氯酸钠溶液对单核细胞释放MMPs的体外活性。
将人单核细胞THP-1(ATCC TIB-202™)细胞系分化为巨噬细胞,并用不同浓度的次氯酸钠(从0.05%至5×10%)进行处理。此外,用处于炎症期的活动性下肢静脉溃疡患者的伤口渗出液(WF)刺激THP-1细胞系。还评估了次氯酸钠(0.025 - 0.0062%)对健康人外周血血清样本的影响。通过明胶酶谱法评估处理对MMP-9明胶酶解活性的影响。通过Pro™ Human MMP 9-plex检测法评估对MMPs释放的影响。还进行了探索性划痕伤口愈合试验。
次氯酸钠溶液降低了MMP-9及其活化形式的明胶酶解活性。在外周血血清中也观察到MMP-9明胶酶解活性的下调。MMPs谱显示在用脂多糖和次氯酸钠溶液处理后,MMP-1的释放减少(<0.05),MMP-9和MMP-12的释放略有减少。在用次氯酸钠溶液激活巨噬细胞并处理后,观察到伤口愈合有轻微改善。
所获得的结果表明次氯酸钠溶液可能具有调节伤口微环境中蛋白水解途径的能力,进一步表征了其在伤口护理临床实践中的活性和用途。