抗血管生成对瘢痕疙瘩成纤维细胞增生和凋亡的影响  

Influence of anti-angiogenesis therapy on proliferation and apoptosis of fibroblasts derived from keloid

作　　者：毛运春[1] 马雪梅[1] 时书舫[1] 高银光[1] 岂红娇[1] 陈书媛[1] 

机构地区：[1]首都医科大学附属北京友谊医院普外科整形外科,北京100050

出　　处：《国际外科学杂志》2011年第7期461-465,F0004,共6页International Journal of Surgery

基　　金：首都医科大学附属北京友谊医院科研启动基金资助项目（No.2008-18）

摘　　要：目的探讨人工抗血管生成对瘢痕疙瘩成纤维细胞的增生和凋亡的影响，为瘢痕疙瘩的抗血管治疗提供实验依据。方法手术切除人瘢痕疙瘩1条，将其分成30块，分别种植于裸鼠皮下，其中24块成活，分成3组，应用促血管内皮生长因子（VEGF组）、血管内皮抑制素（Endostar组）和0．9％的氯化钠溶液（对照组）干预瘢痕疙瘩微血管数量，分别于手术后21、23、25、27d向瘢痕疙瘩周边注射VEGF（0．4mg／0．2mL）、endostar（0．125μg／0．2mL）、0．9％的氯化钠溶液（0．2mL），注射后第10天取材，采用苏木精一伊红染色、免疫组化和末端脱氧核苷酸转移酶介导的末端标记技术，检测24例瘢痕疙瘩中成纤维细胞的增生和凋亡状态，比较各组瘢痕疙瘩组织在增生、凋亡方面的差异。结果对照组PI为（34．75±3．62），AI为（7．88±1．64）、AI／PI为（0．23±0．07），与对照组相比，VEGF组成纤维细胞的增生细胞核增加，PI为（41．13±2．29），凋亡细胞减少，AI为（5．75±1．28），AI／PI为（0．14±0．04）；Endostar组成纤维细胞的增生细胞核减少，PI为（27．25±2．61），凋亡细胞增加，AI为（11．00±1．31），AI／PI为（0．41±0．09）。与对照组相比，成纤维细胞平均增生指数、平均凋亡指数、平均凋亡指数／平均增生指数，差异均有统计学意义。结论抗血管生成抑制成纤维细胞增生诱导其凋亡，有可能是瘢痕疙瘩治疗的新途径。SHI Shu-fang, GAO Yin- guang , QI Hong-fiao , CHEN Shu- yuan. Department of General Surgery and Plastic Surgery, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, China Corresponding author： MAO Yun-chun, Email ： maoyunchun@ sohu. corn [ Abstract] Objective To investigate the influence of anti-angiogenesis therapy on proliferation and ap- optosis of fibroblasts derived from keloids. Methods Thirty pieces of keloids from a patient were implanted into subcutaneous tissue of the nude mice, 24 pieces of which survived were divided into three groups which were treated with perilesional injection of vascular endothelial growth factor（VEGF） （0.4 mg/0.2 mL）, En- dostar（0. 125 g/0. 2 mL） and physiological saline （0.2 mL） on the 21 d, 23 d, 25 d, 27 d after implantation. Sample were collected on the lOth day after perilesional injection, the proliferating fibroblasts in keloid tissue were immunohistochemically detected by proliferating cell nuclear antigen （PCNA） expression. The apoptotic cell was detected by terminal deoxynucleotidyl transferase dUTP-nick end labeling （TUNEL） staining. Results IHC staining indicated that PCNA expression of fibroblasts was significantly increased in keloid tissue after VEGF injection, PCNA expression of fibroblasts was significantly reduced in keloid tissue after Endostar injection, TUNEL assay revealed lower apoptotie cells expression in the keloid tissue after VEGF injection and higher in the Endostar group than control group. The rate of proliferative index （PI）, apoptotic index（Al） and AI/PI of fibroblasts in keloid after VEGF （PI：41.13 ±2.29,AI：5.75 ±1.28,AI/PI： 0. 14 ± 0.04） or Endostar injection （ P1：27.25 ±2.61 ,AI ： 11.00 ± 1.31 ,AI/P1：0.41 ± 0. 09 ） and control group （ PI ： 34.75 ± 3.62,AI：7.88 ± 1.64,AI/PI：0.23 ± 0.07） showed statistical differences. Conclusion Anti-angiogenesis therapy is shown to induce keloid regression through suppression of keloid fibroblast prolif

关 键 词：瘢痕疙瘩 增生 凋亡 

分 类 号：R622[医药卫生—整形外科]