重组人内抑素抑制创面瘢痕增生的实验研究

Study of the inhibitory effects of recombinant human endostatin on hypertrophic scars

目的观察重组人内抑素(rhEndostatin)对兔耳瘢痕增生的抑制作用,探讨其部分作用机制。方法建立兔耳增生性瘢痕(HS)模型,瘢痕块内局部注射rhEndostatin(1.25、2.5、5 g/L),观察瘢痕大体形态及组织学变化,免疫组织化学检测瘢痕组织Ⅰ、Ⅲ型胶原表达,电镜观察瘢痕组织成纤维细胞凋亡。结果与模型组和生理盐水组比较,2.5 g/L和5 g/L rhEndostatin组瘢痕平坦,面积减小,质地变软,瘢痕增生指数降低(P<0.05);微血管密度降低(P<0.05);Ⅰ、Ⅲ型胶原表达水平降低(P<0.05);成纤维细胞凋亡。结论rhEndostatin可抑制HS形成,该作用可能与rhEndostatin抑制血管生成,进而促进增生性瘢痕成纤维细胞(HSFs)凋亡,减少胶原的产生与沉积有关。

Objective To investigate the therapeutic effects of recombinant human endostatin （ rhEndostatin ） on hypertrophic scar （ HS ） and explore the possible mechanism of action involved. Methods A rabbit ear model with hypertrophic scars was established. Recombinant human endostatin injections were applied to the scars of the experimental group topically in different concentrations （1. 25, 2. 5, 5 g/L）. The changes of macroscopic characteristics of scars were examined. Light microscopy and transmission electron microscopy were used for histomorphometric analysis. The levels of collagens Ⅰ and Ⅲ were detected by immunohistochemistry. Results Compared with physiological saline group and model group, group treated with rhEndostatin 2. 5 g/L and 5. 0 g/L showed significant reduction in height, volume and hardness, it resulted in a statistically significant reduction in the scar elevation index, the microvessel density and the expression of type Ⅰ and Ⅲ collagens （P〈0. 05）. An observation under transmission electron microscopy revealed that some fibroblasts nucleus ruptured and disintegrated and apoptotic body were observed in rhEndostatin 5 g/L group, but seldom found in triamcinolone group. Conclusion The findings of this study suggest that rhEndostatin has a markedly inhibitive effect on the formation of hypertrophic scar. It suppresses angiogenesis, and subsequently promotes HSFs apoptosis and reduces the overproduction and excessive deposition of collagen may account for this result.