靶向沉默血管内皮生长因子对兔耳增生性瘢痕的影响

Influences of the targeting silencing vascular endothelial growth factor on the formation of hypertropic scar

目的探讨慢病毒介导的靶向沉默血管内皮生长因子对兔耳增生性瘢痕形成的影响及其可能的作用机制，研究血管靶向基因治疗对兔耳增生性瘢痕的防治作用。方法以10只健康的日本大耳白兔建立兔耳增生性瘢痕模型，并随机选择兔的左、右耳作为实验组和对照组。创面愈合后，实验组注射携带目的基因LV—SiVEGF的重组慢病毒，对照组注射无关的LV—NC空载慢病毒。创面愈合后第30天取材，观察对比各组瘢痕外观形态的变化，并对瘢痕组织进行HE、Masson、CD34、血管内皮生长因子染色及透射电镜观察，研究分析靶向沉默兔耳瘢痕组织中血管内皮生长因子的表达对组织内血管生成及成纤维细胞增殖的影响。结果与对照组相比，实验组血管靶向基因治疗后30d，兔耳增生性瘢痕中微血管生成明显减少、胶原合成及成纤维细胞增殖均受到明显抑制。结论瘢痕形成早期应用基因LV—SiVEGF治疗可明显抑制兔耳增生性瘢痕的形成。

Objective To investigate the effects and possible mechanism of lentivirus-mediated targeting silencing vascular endothelial growth factor on the formation of rabbit ear hypertrophic scar and to explore the effect of vascular targeting gene therapy for prevention against rabbit ears hypertrophic scar. Methods Ten Oryc- tolagus cuniculus were used to establish the rabbit ears hypertrophic scar model. The left and the right ear of an individual rabbit were randomly selected as either the experimental group or the control one. Once the wound healed, the experimental group was injected with recombinant lentivirus carrying the target gene, LV-SiVEGF, while the control group was injected with loadless lentivirus carrying unrelated LV-NC. The samples were harves- ted at 30 days after the wound healed to observe the changes of scar appearance between the two groups and per- form the HE staining, Masson staining, CD34 staining, vascular endothelial growth factor staining and the ultra- structure was studied with transmission electron microscopy （TEM） to investigate the effect of slencing target vas- cular endothelial growth factor gene expression on the angiogenesis and fibroblast proliferation in the rabbit ear scar tissue. Results Contrasted with the control group, the angiogenesis in the hypertrophic scar of rabbit ear was significantly reduced and the collagen synthesis and fibroblast proliferation were inhibited in the experimental group with vessels targeted gene therapy at 30 days. Conclusion Application of LV-SiVEGF gene therapy in the early stage of scar formation can significantly inhibit the formation of hypertrophic scars of rabbit ears.