Chamberlain J, Shah M, Ferguson M W
School of Biological Sciences, University of Manchester, UK.
J Anat. 1995 Feb;186 ( Pt 1)(Pt 1):87-96.
Scarring, leading to impaired function, growth and appearance, is a major problem following many forms of surgery. Fetal wounds, unlike those in the adult, are characterised by a reduced growth factor profile and the absence of scar tissue (Whitby & Ferguson, 1991 a, b). The antiparasitic drug, suramin (a heparin analogue) inhibits binding of various growth factors (e.g. PDGF, bFGF, TGF-beta, EGF, IGF-I, IGF-II) to their receptors in vitro. These growth factors play key roles in wound healing. We attempted to manipulate experimentally their effectiveness in healing adult rat dermal incisional wounds by injecting suramin into the wound margins and comparing the resultant healing with an unmanipulated control wound in the same animal. Immunohistochemical staining demonstrated that, on d 7 and 14 postwounding, the numbers of monocytes/macrophages and blood vessels are markedly increased in suramin treated wounds compared with controls. Extracellular matrix deposition is lower, although very compact in organisation, lacking the usual honeycombed appearance of normal skin. These effects are widespread, being present not only in the wound area, but also in the surrounding tissue. No difference was detected at 70 d postwounding between the scars of suramin-treated and unmanipulated control wounds in the same animals. All such effects are increased slightly through the concentration range of 0.04-40 mg/kg suramin, with no significant change as concentrations greater than 40 mg/kg are applied. This suggests that suramin has marked effects on the early stages of wound healing, which plateau at 40 mg/kg concentration, but has no effect on scar formation.
瘢痕形成会导致功能、生长和外观受损,是多种手术形式后面临的主要问题。与成年个体的伤口不同,胎儿伤口的特征在于生长因子水平降低且无瘢痕组织(惠特比和弗格森,1991a,b)。抗寄生虫药物苏拉明(一种肝素类似物)在体外可抑制多种生长因子(如血小板衍生生长因子、碱性成纤维细胞生长因子、转化生长因子-β、表皮生长因子、胰岛素样生长因子-I、胰岛素样生长因子-II)与其受体的结合。这些生长因子在伤口愈合中起关键作用。我们试图通过向伤口边缘注射苏拉明,并将由此产生的愈合情况与同一只动物中未处理的对照伤口进行比较,来实验性地操控其对成年大鼠皮肤切开伤口愈合的有效性。免疫组织化学染色显示,在受伤后第7天和第14天,与对照相比,苏拉明处理的伤口中单核细胞/巨噬细胞数量和血管数量显著增加。细胞外基质沉积较少,尽管结构非常致密,缺乏正常皮肤通常的蜂窝状外观。这些影响广泛存在,不仅在伤口区域,而且在周围组织中也存在。在受伤后70天,同一只动物中苏拉明处理的伤口瘢痕与未处理的对照伤口瘢痕之间未检测到差异。在苏拉明浓度范围为0.04 - 40 mg/kg时,所有这些影响均略有增加,当应用浓度大于40 mg/kg时无显著变化。这表明苏拉明对伤口愈合的早期阶段有显著影响,在40 mg/kg浓度时达到平稳状态,但对瘢痕形成没有影响。
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