Mwaura B, Mahendran B, Hynes N, Defreitas D, Avalos G, Adegbola T, Adham M, Connolly C E, Sultan S
Department of Vascular and Endovascular Surgery, and Western Vascular Institute, University College Hospital, Galway, Ireland.
Eur J Vasc Endovasc Surg. 2006 Mar;31(3):306-10. doi: 10.1016/j.ejvs.2005.08.007.
Alteration in the expression of extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase-2 (MMP-2), tissue inhibitors of matrix metalloproteinases (TIMP-2) and platelet derived growth factor (PDGF-AA) may contribute to poor healing in venous leg ulcers.
The aim of this study is to determine the expression of EMMPRIN, MMP-2, TIMP-2 and PDGF-AA in the ulcer exudates and perivascular tissue of healing and non-healing chronic venous ulcers.
PATIENTS, MATERIALS AND METHODS: Forty patients with chronic venous ulcers were included in this study, with a mean age of 60 years. Eleven patients were males and 29 were females. All patients had normal ankle brachial index and a venous ulcer of at least 8 weeks duration. Immuno-histochemistry using monoclonal antibodies to PDGF-AA, MMP-2, TIMP-2 and EMMPRIN was carried out on paraffin embedded punch biopsy skin specimens from the ulcer edge. Enzyme linked immunosorbent assay for PDGF, MMP-2 and TIMP-2 were carried out on wound fluids collected from patients. The ulcer size and character at the initial assessment and after 8 weeks were assessed to determine the status of ulcer healing.
No significant difference was seen in the expression of TIMP-2, MMP-2 and EMMPRIN between the two groups. However, in the non-healing group high levels of MMP-2 and low levels of TIMP-2 in the wound fluid suggest a strong correlation of these two markers in the state of healing. Analysis of wound fluid by ELISA demonstrated high PDGF-AA in the healing group (p = 0.021). Significantly increased levels of PDGF-AA (p<0001) was noted in the perivascular area on immuno-histochemistry of healing ulcers. These data suggest that PDGF-AA plays an important role in healing of venous ulcers.
Non-healing venous ulcers are associated with greater activity MMP-2 activity. The ratio of MMPs to their inhibitors TIMPs, dictate the rate of healing of the ulcers. PDGF-AA activity is associated with ulcer healing, though the mechanism is unclear. EMMPRIN expression in chronic venous ulcers probably parallels the chronicity of the condition rather than propagate it. However, further studies with larger samples are needed.
细胞外基质金属蛋白酶诱导剂（EMMPRIN）、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶组织抑制剂（TIMP-2）和血小板衍生生长因子（PDGF-AA）表达的改变可能导致下肢静脉溃疡愈合不良。
本研究旨在确定EMMPRIN、MMP-2、TIMP-2和PDGF-AA在愈合和未愈合的慢性静脉溃疡的溃疡渗出液和血管周围组织中的表达。
患者、材料与方法：本研究纳入40例慢性静脉溃疡患者，平均年龄60岁。男性11例，女性29例。所有患者踝肱指数正常，且静脉溃疡病程至少8周。对溃疡边缘石蜡包埋的打孔活检皮肤标本进行免疫组织化学检测，使用抗PDGF-AA、MMP-2、TIMP-2和EMMPRIN的单克隆抗体。对患者采集的伤口渗出液进行PDGF、MMP-2和TIMP-2的酶联免疫吸附测定。在初始评估时和8周后评估溃疡大小和特征，以确定溃疡愈合状况。
两组之间TIMP-2、MMP-2和EMMPRIN的表达无显著差异。然而，在未愈合组中，伤口渗出液中高水平的MMP-2和低水平的TIMP-2表明这两种标志物在愈合状态中存在强烈相关性。通过酶联免疫吸附测定分析伤口渗出液发现，愈合组中PDGF-AA水平较高（p = 0.021）。在愈合溃疡的免疫组织化学检测中，血管周围区域的PDGF-AA水平显著升高（p<0.001）。这些数据表明PDGF-AA在静脉溃疡愈合中起重要作用。
未愈合的静脉溃疡与更高的MMP-2活性相关。基质金属蛋白酶与其抑制剂基质金属蛋白酶组织抑制剂的比例决定了溃疡的愈合速度。PDGF-AA活性与溃疡愈合相关，但其机制尚不清楚。慢性静脉溃疡中EMMPRIN的表达可能与病情的慢性程度平行，而非促进病情发展。然而，需要更大样本量的进一步研究。
