Objective: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.Methods: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.Results: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.Conclusions: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 fibrobla
Hai-tao RENHang HUYuan LIHong-fei JIANGXin-lei HUChun-mao HAN
