重组人内抑素对兔耳创面瘢痕组织血管内皮生长因子、转化生长因子-β_1和碱性成纤维细胞生长因子表达的影响

Effects of recombinant human endostatin on the expression of vascular endothelial growth factor,transforming growth factor-β_1 and basic fibroblast growth factor on hypertrophic scar in rabbit ears

目的观察重组人内抑素(rh Endostatin)对兔耳创面瘢痕增生及血管内皮生长因子(VEGF)、转化生长因子β1(TGF-β1)和碱性成纤维细胞生长因子(b FGF)表达的影响,探讨rh Endostatin抑制瘢痕增生的分子机制。方法健康新西兰大耳白兔20只,均分为正常对照组、模型组、生理盐水(NS)对照组、rh Endostatin(5 g/L)治疗组和醋酸曲安奈德(TA,40 g/L)对照组;除正常对照组外其余各组均进行增生性瘢痕动物模型的复制,在兔耳腹侧面制作1cm×1cm大小创面。术后第28天,rh Endostatin治疗组瘢痕皮内注射相应浓度rh Endostatin(100μl),NS对照组注射等量生理盐水,隔日1次,共6次;TA对照组瘢痕块内注入相应浓度曲安奈德(100μl),每周1次,共2次;模型组术后不接受处理。术后第47天摄片并收集瘢痕及正常皮肤标本,应用免疫组织化学方法检测VEGF、TGF-β1和b FGF的表达。结果形态学观察结果显示,术后第47天rh Endostatin治疗组瘢痕皮肤色泽变浅,变软变平,体积减小,与模型组和NS对照组比较有明显差异;免疫组织化学检测结果可见,与模型组和NS对照组相比,rh Endostatin治疗组VEGF和TGF-β1蛋白表达减少,b FGF表达增加,差异均具有统计学意义(P<0.01)。结论 rh Endostatin能有效抑制兔耳创面瘢痕增生,其机制可能与rh Endostatin影响VEGF、TGF-β1和b FGF蛋白的表达有关。

Objective To investigate the effect of rhEndostatin on hypertrophic scar in rabbit ears and its mechanism. Methods Twenty healthy New Zealand big-eared white rabbits were divided equally into normal control group, model group, normal saline （NS） control group, rhEndostatin treatment group and triamcinolone acetonide （TA） control group. All groups were reproducing animal model of hyperplastic scar except normal control group, 1 cm× 1 cm size of the wound were made on ventral side of rabbit ears. Treatments were administered starting on postoperative days 28. rhEndostatin （100pal） was injected intradermally into the wounds of rhEndostatin treatment group with scar block local injection, NS control group injected with saline, the injection frequency of the two groups was once every other day for 6 successive times. The wounds treated with TA received the same doses, and the injection frequency was once a week, a total of 2 times. For model group, wounds received no iniections. At postoperative days 47, collected scars and normal skin specimens, observe the change of rabbit ear scar in all groups, and the immunohistochemical method was also used to detect the distribution of vascular endothelial growth factor-β1 （VEGF） , transforming growth factor-β1 （ TGF-β1 ） and basicfibroblast growth factor（bFGF）positive signals. Results The scar morphological change appeared to be smaller, softer,flatter, and lighter in color in the rhEndostatin treatment group than those in the model group and NS control group. The intensities of immunohistoehemieal positive staining for VEGF and TGF-β1 were lower in rhEndostatin treatment group than those in the model group. The bFGF immunohistochemical positive staining intensity was increased significantly （P 〈O. 01）. Conclusion rhEndostatin can inhibit the hypertrophic scar in rabbit ears, the mechanism might be related toexpression of VEGF, TGF-β1 and bFGF.