Inhibition of procollagen C‐proteinase reduces scar hypertrophy in a rabbit model of cutaneous scarring
Inhibition of procollagen C‐proteinase reduces scar hypertrophy in a rabbit model of cutaneous scarring
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DOI：
10.1111/j.1743-6109.2006.00103.x
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发表时间：
2006-03
影响因子：
2.9
通讯作者：
R. Reid;J. Mogford;R. Butt;A. deGiorgio-Miller;Thomas A. Mustoe, MD, FACS
中科院分区：
文献类型：
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作者：
R. Reid;J. Mogford;R. Butt;A. deGiorgio-Miller;Thomas A. Mustoe, MD, FACS
增生性瘢痕是由于真皮伤口修复部位过度的胶原沉积引起的，对手术患者来说，在功能和美观上都会减弱。药物调节胶原的合成和沉积是控制瘢痕组织形成的直接途径。胶原稳定的关键步骤之一是C末端前肽从前体分子中裂解形成胶原纤维，这一反应是由前胶原C-蛋白酶(PCP)催化的。我们在兔耳模型上测试了PCP抑制剂减少增生性瘢痕形成的能力。新西兰大白兔每耳放置4个7 mm真皮创面，伤后7、9、11、13天(早期治疗，n=20个创面)或11、13、15、17天(晚期治疗，n=20个创面)左耳皮下注射PCP抑制剂。每只动物的右耳作为对照(单独作为交通工具)。术后第28天取创面，通过测量瘢痕抬高指数量化瘢痕肥大程度。与对照组相比，早期使用PCP抑制剂治疗创面并不能减少瘢痕形成(p>；0.05)。然而，晚期治疗导致瘢痕升高指数在统计学上显著降低(p<；0.01)。我们的结果不仅指出了PCP抑制剂用于减轻增生性瘢痕的潜在用途，也指出了药物输送在抗瘢痕治疗中的临时重要性。
Hypertrophic scarring, which results from excessive collagen deposition at sites of dermal wound repair, can be functionally and cosmetically debilitating to the surgical patient. Pharmacological regulation of collagen synthesis and deposition is a direct approach to the control of scar tissue formation. One of the key steps in collagen stabilization is the cleavage of the C‐terminal propeptide from the precursor molecule to form collagen fibrils, a reaction catalyzed by procollagen C‐proteinase (PCP). We tested the ability of a PCP inhibitor to reduce hypertrophic scar formation in a rabbit ear model. After the placement of four, 7‐mm dermal wounds on each ear, New Zealand white rabbits received PCP inhibitor subcutaneously in the left ear at four time points postwounding: days 7, 9, 11, 13 (early treatment; n=20 wounds) or days 11, 13, 15, 17 (late treatment; n=20 wounds). The right ear of each animal served as a control (vehicle alone). Wounds were harvested on postoperative day 28 and scar hypertrophy quantified by measurement of the scar elevation index. Early treatment of wounds with PCP inhibitor did not reduce scar formation compared with controls (p>0.05). However, late treatment resulted in a statistically significant reduction in the scar elevation index (p<0.01). Our results point not only to the potential use of PCP inhibitors to mitigate hypertrophic scarring but also to the temporal importance of drug delivery for antiscarring therapy.