维A酸涂膜剂对兔耳早期增生性瘢痕的影响

Effect of tretinoin gel sheeting on early-stage hyperplastic scars in rabbit ears

目的研究维A酸涂膜剂对兔耳早期增生性瘢痕的影响，探讨其防治瘢痕的可行性。方法选取新西兰白兔24只，建立兔耳增生性瘢痕模型后，随机分为4组，每组6只。A组：对照组，B组：涂膜剂组，C组：0．05％维A酸涂膜剂组，D组：0．1％维A酸涂膜剂组，连续用药6周，期间观察记录瘢痕大小、厚度、颜色、硬度，6周后分别切取兔耳瘢痕组织，HE染色，胶原染色（VG法），行病理学观察、检测及分析。结果A组瘢痕颜色深、厚而硬，并明显高于皮肤，表面凹凸不平；B组、C组、D组瘢痕颜色浅，质地软，厚度薄，皮下结节小，其中C、D组与周围正常皮肤接近，D组瘢痕表面有脱皮现象。HE、VG染色中，A组胶原排列紊乱，有旋涡状结构；C组和D组单位面积内成纤维细胞、微血管数量、胶原沉积量较A组和B组少，且胶原排列整齐，与瘢痕长轴平行。瘢痕增生指数（HI）：A组3．17±0．26，B组2．46±0．19，C组1191±0．21，D组1．90±0．23；成纤维细胞密度（NA）：A组5836．70±527．03，B组4128．73±387．66，C组3207．59±439．17，D组3200．28±421．48；胶原纤维的面密度（AA）：A组45．38±5．83，B组36．57±6．84，C组28．09±3．82，D组28．07±3．47。A组与B、C、D组比较，HI、NA、AA值差异均有统计学意义（P〈0．01）；B组与C、D组比较，HI、NA、AA值差异均有统计学意义（P〈0．01）；C组与D组比较，HI、NA、AA值差异无统计学意义（P〉0．05）。结论维A酸涂膜剂可以抑制兔耳早期瘢痕增生，可为防治瘢痕提供一种新的外用方法。

Objective To estimate the effect of tretinoin gel sheeting on early-stage hyperplastic scars in rabbit ears, and to evaluate the feasibility to prevent and treat hyperplastic scars with it. Methods The ears of 24 rabbits were used to establish a model of hyperplastic scar according to previously reported methods. Then, the rabbit ears were randomly divided into four groups： control group receiving no treatment, gel sheeting group treated with the vehicle of the tretinoin gel sheeting, 0.05% tretinoin group treated with 0.05% tretinoin gel sheeting, 0.1% tretinoin group treated with 0.1% tretinoin gel sheeting. All the gel sheetings were topically used twice daily for six consecutive weeks. During the treatment, the size, thickness, color and texture of scars were estimated. After six weeks of treatment, all the scar tissues were resected from the rabbit ears and subjected to hematoxylin and eosin （HE） staining and van Gieson （VG） staining. Statistical analysis was carried out by analysis of variance and rank sum test. Results The scars were deeply colored, thickened, hard and elevated with an uneven surface in the control group, but lightly colored, thinned and soft with the presence of small subcutaneous nodules in the other three groups. The surface of scars in the two tretinoin groups was similar to that of adjacent normal skin, and scaling was observed on the scar surface in the 0.1% tretinoin group. HE and VG staining showed a disarrangement of collagen fibers with the formation of vortex-like structures in the control group. A significant decrease was noted in the number of fibroblasts and microvessels as well as amount of collagen deposition per unit cross-sectional area in the two tretinoin groups compared with the control group and gel sheeting group. Additionally, the collagen fibers were regularly arranged and parallel to the long axis of scars in the two tretinoin groups. The scar hyperplasia index （HI） was 3.173 ± 0.26, 2.465 ± 0.19, 1.906± 0.21 and 1.903 ±0.23 in the control group, gel sheeting group, 0.05% tretinoin group and 0.1% tretinoin group respectively, the fibroblast density （NA） was 5836.7± 527.03, 4128.73 ± 387.66, 3207.59 ± 439.17 and 3200.28 ± 421.48 respectively, and the area density of collagen fiber （AA） was 45.38 ±5.83, 36.57 ± 6.84, 28.09 ± 3.82 and 28.07 ± 3.47 respectively. As far as HI, NA and AA were concerned, the control group differed significantly from the other three groups （all P 〈 0.01 ）, and the gel sheeting group from the two tretinoin groups （all P 〈 0.01）, but no significant difference was observed between the two tretinoin groups （all P 〉 0.05）. Conclusions Topical tretinoin gel sheeting can inhibit scar proliferation at early stage in rabbit ears, and may provide a new choice for the prevention and treatment of hyperplastic scars.