Trøstrup Hannah, Holstein Per, Karlsmark Tonny, Moser Claus, Ågren Magnus S
Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Copenhagen Wound Healing Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
J Wound Care. 2018 Nov 2;27(11):724-734. doi: 10.12968/jowc.2018.27.11.724.
To compare matrix metalloproteinase (MMP)-9 and the antiproteinase tissue inhibitor of metalloproteinases (TIMP)-1 in wound fluids and sera from patients with chronic non-healing or acute healing wounds. In addition, the functional consequences on MMP-9 activity and general gelatinase activity were assessed.
In this observational study, samples were collected from patients with venous leg ulcers (VLUs), patients with type 2 diabetes with neuropathic foot ulcers (DFUs), and from another cohort of VLU patients with sterile split-thickness skin graft donor sites after autologous skin grafting, serving as healing control wounds. MMP-9 and TIMP-1 concentrations were determined by enzyme-linked immunosorbent assays. MMP-9 and gelatinase activities were determined in wound fluids in subsets of the patients.
A total of 24 patients took part in the study. No significant differences in MMP-9 wound fluid levels were found among the three groups. TIMP-1 levels were markedly and significantly lower in the two chronic wound groups resulting in a severely unbalanced MMP-9/TIMP-1 ratio, especially notable in the VLU group and possibly in the elevated endogenous MMP-9 activity (p<0.01) compared with the acute wound fluids. At least 20% of the chronic wound fluids displayed atypical patterns on gelatin zymography and showed high general gelatinase activity that was not inhibited by either TIMP-1 or by a gelatinase inhibitor (AG3340). MMP-9 levels were higher in the sera of the patients with type 2 diabetes.
We hypothesise that non-MMP proteinases contribute to matrix destruction in a significant number of chronic wounds. Blocking the excessive MMP-9 activity may be insufficient to normalise wound healing. The reasons and effects of the very low TIMP-1 levels in chronic wounds need further clarification.
比较慢性不愈合伤口或急性愈合伤口患者伤口渗出液和血清中的基质金属蛋白酶（MMP）-9及金属蛋白酶组织抑制因子（TIMP）-1。此外，评估其对MMP-9活性和一般明胶酶活性的功能影响。
在这项观察性研究中，收集了患有下肢静脉溃疡（VLU）的患者、患有2型糖尿病并伴有神经性足部溃疡（DFU）的患者，以及另一组自体皮肤移植后具有无菌中厚皮片供皮区的VLU患者的样本，后者作为愈合对照伤口。通过酶联免疫吸附测定法测定MMP-9和TIMP-1的浓度。在部分患者的伤口渗出液中测定MMP-9和明胶酶活性。
共有24名患者参与了该研究。三组之间MMP-9伤口渗出液水平未发现显著差异。在两个慢性伤口组中，TIMP-1水平明显且显著降低，导致MMP-9/TIMP-1比例严重失衡，在VLU组尤为明显，与急性伤口渗出液相比，内源性MMP-9活性可能升高（p<0.01）。至少20%的慢性伤口渗出液在明胶酶谱上显示出非典型模式，并表现出高一般明胶酶活性，该活性不受TIMP-1或明胶酶抑制剂（AG3340）抑制。2型糖尿病患者血清中的MMP-9水平较高。
我们推测，在大量慢性伤口中，非MMP蛋白酶对基质破坏有显著作用。阻断过度的MMP-9活性可能不足以使伤口愈合正常化。慢性伤口中TIMP-1水平极低的原因和影响需要进一步阐明。
