ASSESSMENT OF DIFFERENTIAL CYTOKINE EFFECTS ON ANGIOGENESIS USING AN IN-VIVO MODEL OF CUTANEOUS WOUND REPAIR
ASSESSMENT OF DIFFERENTIAL CYTOKINE EFFECTS ON ANGIOGENESIS USING AN IN-VIVO MODEL OF CUTANEOUS WOUND REPAIR
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DOI：
10.1006/jsre.1995.1071
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发表时间：
1995-05-01
影响因子：
2.2
通讯作者：
NANNEY, LB
中科院分区：
文献类型：
--
作者：
ROESEL, JF;NANNEY, LB
血管生成，或称新血管形成，近年来一直是一个密集的研究主题。这项研究的一个主要障碍是选择一个合适的体内模型来与人类进行比较，以及一个可靠的定量方法。利用猪切除创面愈合模型，我们报道了一种新的、简单的技术，可以获得对微血管间隔的客观评估。利用组织学标本因子免疫组织化学染色，在不受背景干扰的情况下，对内皮细胞进行特异性鉴定。该技术与形态计量学分析相结合，定量检测了肿瘤坏死因子α、转化生长因子β、碱性成纤维细胞生长因子、胰岛素样生长因子-1和表皮生长因子在猪创面愈合中的不同作用。所有细胞因子都能刺激血管生成，其中小剂量的肿瘤坏死因子α和碱性成纤维细胞生长因子在伤后7天表现出最明显的作用。随着肿瘤坏死因子α水平的增加(1 ng、10 ng、100 ng和2.5微克)，微血管面积逐渐减少。尽管碱性成纤维细胞生长因子治疗后在血管生成方面没有明显的剂量反应差异，但毛细血管面积显著增加。在使用EGF或IGF-1治疗后，毛细血管面积显著增加，但不那么显著。比较创伤后7天和10天转化生长因子β对血管生成的影响，发现随着创面成熟，微血管明显减少。我们的数据与以往定性的体外和体内报道一致，从而证实了这一新模型的有效性。这些数据进一步提供了在临床相关的皮肤创伤修复模型中对细胞因子的不同血管生成反应的第一个定量证据。(C)1995年学术出版社。
Angiogenesis, or new blood vessel formation, has been a subject of intense investigation in recent years. A major obstacle in this research has been the selection of an appropriate in vivo model with which comparisons to humans can be made as well as a reliable quantitative method. Using the porcine excisional wound healing model, we report a new and simple technique for obtaining objective assessments of the microvascular compartment. Factor VIII immunostaining of histological specimens was utilized for specific identification of endothelium devoid of background interference. This technique was coupled with morphometric analysis to quantitate the differential effects of tumor necrosis factor alpha (TNF alpha), transforming growth factor beta (TGF beta), basic fibroblast growth factor (bFGF), insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) within healing porcine wounds. All cytokines stimulated angiogenesis, with low dose TNF alpha and bFGF treatments exhibiting the most profound effects at 7 days postwounding. With increasing levels of TNF alpha (1 ng, 10 ng, 100 ng, and 2.5 mu g), a stepwise decrease in microvascular area was noted. Although no significant dose responsive differences in angiogenesis were noted following bFGF treatments, a profound increase in capillary area was shown. Significant yet less dramatic increases were noted in capillary area following treatment with EGF or IGF-1. Comparison of the angiogenic effects of TGF beta at 7 and 10 days postwounding showed a significant decrease in the microvasculature as wounds matured. Our data are consistent with previous qualitative in vitro and in vivo reports, thereby confirming the validity of this new model. The data furthermore provide the first quantitative evidence of differential angiogenic responses to cytokines within a clinically relevant model of cutaneous wound repair. (C) 1995 Academic Press, Inc.