›› 2011, Vol. 31 ›› Issue (12): 1672-.doi: 10.3969/j.issn.1674-8115.2011.12.003

• 论著(基础研究) • 上一篇    下一篇

内皮抑素局部注射对兔耳增生性瘢痕的影响

王西樵, 刘英开, 宋 菲, 徐连菊, 青 春, 陆树良   

  1. 上海交通大学 医学院附属瑞金医院灼伤整形科上海市烧伤研究所, 上海 200025
  • 出版日期:2011-12-28 发布日期:2012-01-04
  • 作者简介:王西樵(1969—), 男, 主治医师, 博士;电子信箱: wxqiao2002@hotmail.com。
  • 基金资助:

    国家重点基础研究发展计划(“九七三”计划)(2005CB522603);国家自然科学基金(30872686)

Effect of local injection of endostatin on hypertrophic scar of rabbit ear

WANG Xi-qiao, LIU Ying-kai, SONG Fei, XU Lian-ju, QING Chun, LU Shu-liang   

  1. Department of Burns and Plastic Surgery, Shanghai Burns Institute, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2011-12-28 Published:2012-01-04
  • Supported by:

    National Key Basic Research Program of China, “973” Program, 2005CB522603;National Natural Science Foundation of China, 30872686

摘要:

目的 探讨内皮抑素局部注射对兔耳增生性瘢痕的影响及其机制。方法 建立兔耳增生性瘢痕模型,于建模后第4周,右侧兔耳瘢痕组织内注射内皮抑素(实验组,n=10),左侧兔耳瘢痕组织内注射生理盐水(对照组,n=10),每周注射1次,连续注射3次;于建模后第7周,分别采集实验组和对照组兔耳瘢痕组织,苏木精-伊红染色观察瘢痕组织形态学改变,免疫组织化学法检测微血管标志物CD34表达,TUNEL法检测成纤维细胞凋亡。体外培养脐静脉内皮细胞,分别将不同浓度的内皮抑素加入Martrigel培养体系中,观察内皮细胞在Martrigel上形成微血管管腔数目的变化。结果 与对照组比较,实验组增生性瘢痕缩小明显,紫红色逐渐减退,瘢痕组织内成纤维细胞数量减少,胶原疏松。实验组兔耳瘢痕组织内CD34阳性细胞百分比显著少于对照组,分别为(2.21±0.39) %和(6.11±1.32) %(P<0.05),凋亡细胞百分比明显高于对照组,分别为(9.06±1.54)%和(5.21±1.11) %(P<0.05)。体外实验观察发现:在未加入内皮抑素的Martrigel培养体系中,内皮细胞形成较多微血管分支,随着内皮抑素质量浓度的提高,微血管形成管腔的数目逐渐减少。结论 内皮抑素局部注射具有抑制增生性瘢痕形成并促进其成熟消退的作用,其机制可能与抑制微血管形成有关。

关键词: 增生性瘢痕, 内皮抑素, 瘢痕消退, 微血管

Abstract:

Objective To investigate the effect of local injection of endostatin on hypertrophic scar of rabbit ear, and explore the mechanism. Methods Models of hypertrophic scar of rabbit ear were established. Four weeks after model establishment, scar tissues of right rabbit ears were injected with endostatin once a week for three weeks (experiment group, n=10), and scar tissues of left rabbit ears were injected with normal saline once a week for three weeks (control group,  n=10). Seven weeks after model establishment, scar tissues of rabbit ears in experiment group and control group were obtained, histomorphological changes were observed with HE staining, expression of microvessel marker CD34 was determined by immunohistochemistry, and apoptosis of fibroblasts was detected by TUNEL. Umbilical endothelial cells were cultured in vitro and seeded on Martrigel culture system with different concentrations of endostatin, and vessel tube formation of endothelial cells was observed. Results Compared with control group, the area of hypertrophic scar in experiment group significantly reduced, the number of fibroblasts in scar tissues decreased and collagen density became loose. The percent of cells with positive expression of CD34 in scar tissues in experiment group was significantly lower than that in control group [(2.21±0.39)% vs (6.11±1.32)%, P<0.05], while the percent of  apoptotic cells in experiment group was significantly higher than that in control group [(9.06±1.54)% vs (5.21±1.11)%, P<0.05]. In vitro observation revealed that more microvessel branches formed in Martrigel culture system without endostatin, and the number of microvessel tube formation gradually decreased with the increase of mass concentration of  endostatin. Conclusion Local injection of endostatin may inhibit hypertrophic scar development and promote scar regression, which may be correlated with the inhibition of microvessel tube formation.

Key words: hypertrophic scar, endostatin, scar regression, microvessel