Adenovirus-mediated METH1 gene expression inhibits hypertrophic scarring in a rabbit ear model
Adenovirus-mediated METH1 gene expression inhibits hypertrophic scarring in a rabbit ear model
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腺病毒介导的 METH1 基因表达抑制兔耳模型中的肥厚性疤痕形成
DOI：
10.1111/j.1524-475x.2009.00514.x
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发表时间：
2009-07-01
影响因子：
2.9
通讯作者：
Lu, Kaihua
中科院分区：
文献类型：
--
作者：
Song, Baoqiang;Zhang, Wei;Lu, Kaihua
对于经历过手术或烧伤的患者来说，增生性疤痕仍然是一个主要问题。血管化在增生性瘢痕形成的早期阶段起着重要作用。因此，抑制血管生成可作为一种预防策略。在这项研究中，我们评估了腺病毒介导的METH1（金属蛋白酶和血小板spondin1）基因表达引起的抗血管生成对兔耳增生性瘢痕模型中增生性瘢痕形成的影响。我们首先在上皮化后的第10天、30天、60天和90天对未处理疤痕的微血管和微循环灌注数量进行了研究。在治疗后第30天和第60天，通过计算瘢痕升高指数、计数微血管和亲银核仁组织者区颗粒、检测胶原蛋白的数量，检测腺病毒介导的METH1表达对增生性瘢痕形成的抑制作用。我们发现，未经处理的瘢痕组织在增殖期（上皮化后10-60天）微血管密度和微循环灌注明显高于成熟期（上皮化后90天）（p < 0.05）。治疗后第30、60天，治疗组增生性瘢痕形成明显受到抑制。瘢痕升高指数、微血管计数、亲银核仁组织区数量和总胶原含量均显著降低。我们的研究结果表明，METH1对增生性瘢痕的形成有明显的抑制作用，因此在预防人类增生性瘢痕方面可能有很好的应用前景。
Hypertrophic scarring remains a major problem for patients who have suffered from surgeries or burns. Vascularization plays an important role in the early phase of hypertrophic scarring. Therefore, the inhibition of angiogenesis might be used as a preventive strategy. In this study, we assessed the effect of anti-angiogenesis resulting from adenovirus-mediated METH1 (metalloprotease and thrombospondin1) gene expression on the hypertrophic scar formation in a rabbit ear model of hypertrophic scarring. We first investigated the number of microvessel and microcirculatory perfusion in untreated scars on days 10, 30, 60, and 90 after epithelialization. Then, we examined the effect of anti-angiogenesis by adenovirus-mediated METH1 expression on hypertrophic scar formation by calculating the scar elevation index, counting the microvessel and argyrophilic nucleolar organizer region particle, and detecting the amount of collagen on days 30 and 60 after treatment. We found that untreated scar tissues at the proliferative phase (days 10-60 after epithelialization) had a significantly higher density of microvessel and microcirculatory perfusion than those at the mature phase (day 90 after epithelization) (both p < 0.05). On days 30 and 60 after treatment, the hypertrophic scar formation was significantly inhibited in the treatment group. There was significantly reduced scar elevation index, microvessel count, number of argyrophilic nucleolar organizer region, and total collagen content for treated scars. Our results demonstrate that METH1 has a markedly inhibitive effect on the formation of hypertrophic scar, and may thus have a promising application in the prevention of human hyperthropic scars.