Department of Burns and Wound Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
J Zhejiang Univ Sci B. 2013 Mar;14(3):224-30. doi: 10.1631/jzus.B1200077.
The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation.
Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed (about 15 d post wounding). For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding.
Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 (p<0.05). Scar thickness, measured by scar elevation index (SEI) at Day 35 post wounding, was significantly reduced in the intervention group (1.09±0.19) compared with the controls (1.36±0.28). Microvessel density (MVD) observed in the intervention group (1.73±0.94) was significantly lower than that of the control group (5.63±1.78) on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin.
Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF), thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.
本研究旨在利用兔耳增生性瘢痕模型，研究内皮抑素全身给药抑制瘢痕形成的效果。
将 8 只雄性新西兰白兔随机分为两组。每组兔耳制作 6 个全层皮肤缺损创面，造模后第 15 天（创面愈合后）开始干预，实验组每天给予腹腔注射内皮抑素，对照组给予等量生理盐水。分别于造模后第 15、21、28、35 天用游标卡尺测量各组瘢痕厚度，激光多普勒血流仪评估瘢痕微循环灌注。第 35 天处死白兔，取其瘢痕组织行组织学和蛋白质组学分析。
大体观察发现对照组兔耳瘢痕较实验组厚。两组在第 21、35 天差异有统计学意义（p<0.05）。实验组第 35 天瘢痕隆起指数（SEI）为 1.09±0.19，显著低于对照组的 1.36±0.28。实验组第 35 天微血管密度（MVD）为 1.73±0.94，显著低于对照组的 5.63±1.78。实验组瘢痕内胶原纤维分布较规则，对照组未见胶原纤维排列紊乱。Western blot 分析显示，实验组Ⅰ型胶原和 Bcl-2 表达下调。
本研究通过兔耳增生性瘢痕模型，发现全身应用内皮抑素可抑制局部增生性瘢痕形成，可能是通过减少瘢痕血管生成和血管生成来实现的。本研究结果表明，内皮抑素可能通过促进内皮细胞凋亡和阻断其血小板衍生生长因子（PDGF）和成纤维细胞生长因子（FGF）的释放，从而控制成纤维细胞胶原的产生。血管靶向治疗可能是一种有前途的瘢痕治疗策略。
