重组人血管内皮抑制素对兔耳增生性瘢痕VEGF和TIMP-1表达的影响

目的探讨重组人血管内皮抑制素作用于兔耳增生性瘢痕后对瘢痕中血管内皮生长因子(VEGF)和基质金属蛋白酶抑制剂1(TIMP-1)表达的影响。方法新西兰大白兔16只,建立兔耳增生性瘢痕动物模型。模型建立成功后,将其随机分为实验组和对照组,每组8只。实验组瘢痕局部注射0.1 mL 5 mg/mL的重组人血管内皮抑制素,隔日1次,共5次;对照组局部注射0.1 mL生理盐水,隔日1次,共5次。在药物干预30 d后观察瘢痕大体变化并留取标本,用RT-PCR方法检测VEGF和TIMP-1 mRNA表达水平的变化,用免疫组织化学方法检测瘢痕组织中TIMP-1蛋白表达水平的变化。结果药物干预30 d后实验组兔耳瘢痕中VEGF和TIMP-1 mRNA表达量分别为0.279 0±0.030 7、0.244 4±0.057 4,对照组分别为0.657 0±0.161 1、0.730 2±0.103 8,实验组表达水平均低于对照组(P<0.05)。实验组兔耳瘢痕中TIMP-1蛋白阳性表达水平低于对照组(P<0.05)。结论重组人血管内皮抑制素能抑制兔耳增生性瘢痕组织形成,其机制可能与抑制VEGF和TIMP-1表达有关。

Effect of recombinant human endostatin on VEGF and TIMP-1 expression in hypetrophic scar of rabbit ears

Objective To investigate the effect of recombinant human endostatin on the expression of vascular endothelial growth factor (VEGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in hypertrophic scar (HS) of rabbit ears. Methods A total of 16 New Zealand rabbits were used to establish ear HS models. The model rabbits were evenly randomized into two groups: experimental group and control group. Rabbits in the experimental group were locally injected with recombinant human endostatin (0.1 mL, 5 mg/mL, every other day for five times) and those in the control group were injected with normal saline (0.1 mL, every other day for five times). The HS specimens were harvested 30 days after intervention and were grossly observed; RT-PCR was used to test the expression of VEGF and TIMP-1 mRNA, and TIMP-1 protein was examined by immunohistochemistry method. Results The mRNA expression levels of VEGF and TIMP-1 in experimental group were significantly lower than that in control group (VEGF: 0.279 0±0.030 7 vs 0.657 0±0.161 1, P<0.05; TIMP-1: 0.244 4±0.057 4 vs 0.730 2±0.103 8, P<0.05). The protein expression level of TIMP-1 in experimental group was significantly lower than those in control group (P<0.05). Conclusion Recombinant human endostatin can inhibit HS of rabbit ear, which might be through suppressing the expression of VEGF and TIMP-1.