他克莫司抑制兔耳瘢痕增生的作用及其机制研究

Tacrolimus inhibit scar formation in rabbit ear hypertrophic scar model

目的:他克莫司是临床广泛应用的一种药物,其对增生性瘢痕是否产生作用并无相关报道,为此提出并证实了他克莫司可以抑制兔耳瘢痕增生。方法:建立兔耳增生性瘢痕模型,选10只新西兰大耳白兔双耳腹侧用打孔器制作直径1cm圆形创面,伤后14天创面上皮化后给药,每只兔左耳为空白对照组涂等剂量凡士林软膏,右耳为他克莫司治疗组。分别在伤后14天、21天2、8天3、5天和49天采集标本,行HE染色,观察形态学差异;Real-t i me PCR检测纤维化相关因子TGF-β1、TGF-β2、Col l agen-α1等的表达。结果:HE染色可见他克莫司组成纤维细胞数量及胶原纤维较对照组明显减少,PCR结果可见TGF-β1、TGF-β2及Col l agen-α1表达较对照组在各时间点均减少。结论:实验组较对照组瘢痕明显减轻,证明他克莫司显著抑制兔耳瘢痕增生,可作为临床上治疗及预防瘢痕增生的全新疗法。

Objective Tacrolimus was widly used to inhibit rejection of allograft and therapy for various cutaneous diseases;however,there is no report about its effection on hypertrophic scar.Methods 10 New Zealand White rabbits were randomly divided into two groups with each ear created four wounds use 1cm diameter punch biopsy at standardised locations on the ventral surface.The right ear wounds were taked by tacrolimus ointment 0.1g per wound twice daily started on day 14 postwounding,the left ears were treated with vaseline at the same time.Experimental and control wounds were harvested on days 14,21,28,35 and 49 post wounding,examined histologically to quantify scar elevation index（SEI）.Hematoxylin-eosin staining was performed to reveal differences in scar morphology.Real-time PCR was adopted to measure the variation tendency of the TGF-β1,TGF-β2 and Collagen-α1.Results SEI was significantly reduced after tacrolimus treated versus the applied of Vaseline（P0.05）.Collagen fibrils were thick and rough in the morphological observation.The expression TGF-β1,TGF-β2 and Collagen-α1 could be detected with a distinctly down-regulated in tacrolimus treated group.Conclusion The relief of hypertrophic scar after treatment with tacrolimus in rabbit ear model suggests that tacrolimus might be a novel therapeutic method for hypertrophic scar.