A型肉毒素对兔耳增生性瘢痕的抑制作用及机制

Inhibitory Effect and Mechanism of Botulinum Toxin Type A on Hypertrophic Scar in Rabbit Ears

目的探讨A型肉毒素对兔耳增生性瘢痕的抑制作用及可能的机制。方法SPF级大耳兔建立增生性瘢痕动物模型,随机分成3组:A型肉毒素组(A组)、复方倍他米松组(B组)和对照组(C组)。A、B两组待瘢痕增生达到高峰即伤后第30天,均瘢痕内注入药物,每个创面0.1 mL/次,2周/次,共注射2次,而C组不做任何治疗。于伤后第58天切取兔耳创面作为标本,对比3组瘢痕增生指数、胶原容积分数、血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)、转化生长因子-β1(transforming growth factor beta 1,TGF-β1)及神经肽P物质(neuropeptide substance P,SP)表达的差异。结果A、B、C三组的瘢痕增生指数分别为(1.20±0.15)mm、(1.17±0.10)mm和(2.64±0.34)mm;胶原容积分数为(63.67±2.25)%、(62.08±2.19)%和(79.08±4.80)%;VEGF的表达分别为(24.44±2.62)%、(23.75±2.58)%和(34.39±2.49)%;TGF-β1的表达分别为(23.31±1.86)%、(21.69±2.57)%和(31.67±2.53)%;SP的表达分别为(31.06±3.16)%、(33.17±2.31)%和(43.08±3.32)%,差异均具有统计学意义(P<0.05)。结论A型肉毒素能有效抑制兔耳增生性瘢痕,且可改善痛痒症状,其初步作用机制可能与抑制成纤维细胞增生、降低胶原容积和抑制瘢痕组织中的VEGF、TGF-β1及SP的表达有关。

Objective To investigate the inhibitory effect of botulinum toxin type A on hypertrophic scar of rabbit ear and the possible mechanism.Methods The rabbit ear model of hypertrophic scar was established and randomly divided into three groups:Botulinum toxin A group(group A),compound betamethasone group(group B)and control group(group C).Drug with dose 0.1 mL was injected into scar for both group A and group B after scar hyperplasia reached its peak at the 30 days after modeling,once every two weeks,two times in total.Meanwhile,group C did not receive any treatment.On the 58th day after modeling,the rabbit ear wound was taken as specimen.The scar hyperplasia index,collagen volume fraction,vascular endothelial growth factor(VEGF),transforming growth factor beta-1(TGF-β1)and neuropeptide substance P(SP)were compared among the three groups.Results The scar hyperplasia indexes of group A,B and C were(1.20±0.15)mm,(1.17±0.10)mm and(2.64±0.34)mm,respectively;collagen volume fraction were(63.67±2.25)%,(62.08±2.19)%and(79.08±4.80)%;the expressions of VEGF were(24.44±2.62)%,(23.75±2.58)%and(34.39±2.49)%,respectively;the expression of TGF-β1 were(23.31±1.86)%,(21.69±2.57)%and(31.67±2.53)%,respectively;the expression of SP were(31.06±3.16)%,(33.17±2.31)%and(43.08±3.32)%,respectively.There are significant statistical differences(P<0.05).Conclusion Botulinum toxin A can effectively inhibit hyperplastic purpura in rabbit ears and improve itching symptoms.The mechanism might be inhibition of fibroblasts proliferation,decreasing collagen volume and inhibiting the expression of VEGF,TGF-β1 and SP in scar tissue.