中华皮肤科杂志 ›› 2022, Vol. 55 ›› Issue (8): 720-726.doi: 10.35541/cjd.20210690

• 研究报道 • 上一篇    下一篇

多磺酸黏多糖乳膏对兔耳增生性瘢痕的抑制作用及机制研究

竞艳1    费文敏2    李承旭2    崔勇1，2   

  1. 1安徽医科大学第一附属医院皮肤病与性病科，合肥  230032；2中日友好医院皮肤病与性病科，北京  100029
  • 收稿日期:2021-09-18 修回日期:2021-12-28 发布日期:2022-08-02
  • 通讯作者: 崔勇 E-mail:wuhucuiyong@vip.163.com
  • 作者简介:22年2月份能否见刊？
  • 基金资助:
    国家自然科学基金（81872516）；北京市科委医药协同科技创新研究项目（Z191100007719001）

Inhibitory effect of mucopolysaccharide polysulfate cream on hypertrophic scar formation in a rabbit ear model and its mechanisms of action

Jing Yan1, Fei Wenmin2, Li Chengxu2, Cui Yong1,2   

  1. 1Department of Dermatology and Venereology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, China; 2Department of Dermatology and Venereology, China-Japan Friendship Hospital, Beijing 100029, China
  • Received:2021-09-18 Revised:2021-12-28 Published:2022-08-02
  • Contact: Cui Yong E-mail:wuhucuiyong@vip.163.com
  • Supported by:
    National Natural Science Foundation of China （81872516）; Medical Collaborative Science and Technology Innovation Research Project of Beijing Municipal Science and Technology Commission  （Z191100007719001）

PDF

15

PDF (Mobile)

0

摘要： 【摘要】 目的 探究多磺酸黏多糖乳膏对增生性瘢痕形成的抑制作用及机制。方法 在新西兰白兔（16只）双耳建立直径6 mm的圆形全层创面，构建兔耳增生性瘢痕模型，每只兔耳3个瘢痕创面，左耳瘢痕作为多磺酸黏多糖乳膏实验组，右耳瘢痕为基质对照组，分别外涂多磺酸黏多糖乳膏和基质乳膏，1只兔耳用药量约0.4 g，2次/d，连续6周。分别在用药开始第0天（手术14 d）、14天（手术后28 d）和42天（手术后56 d）取瘢痕组织进行HE染色、Masson染色和免疫组化实验，评估组织病理评分，检测瘢痕厚度、胶原纤维密度和Ⅰ、Ⅲ型胶原蛋白表达及Ⅰ/Ⅲ型胶原蛋白比值。采用t检验和单因素方差分析比较两组各指标差异。结果 HE染色结果显示，与给药前相比，给药42 d对照组存在大量细胞外基质沉积、炎症细胞浸润和局部充血等，而实验组未见明显改变 。给药0、14、42 d，对照组兔耳瘢痕组织病理结构评分明显升高，分别为4.16 ± 1.61、6.50 ± 1.46、6.53 ± 1.34（F = 13.69，P = 0.001），而实验组无明显变化（4.65 ± 1.52、5.13 ± 1.83、5.38 ± 1.60；F = 0.78，P > 0.05）。Masson染色结果显示，给药42 d对照组胶原纤维含量极高，被染成深蓝色，而实验组胶原纤维含量有所下降 ；随着给药时间的增加，与给药前相比，对照组瘢痕组织厚度明显增加（F = 5.64，P = 0.007），而实验组无明显变化（F = 1.48，P > 0.05）。免疫组化结果显示，与给药0 d相比，实验组和对照组各时点Ⅲ型胶原蛋白表达均无明显改变（F = 0.22、0.92，均P > 0.05），但对照组Ⅰ型胶原蛋白表达和Ⅰ/Ⅲ型胶原蛋白比例明显上升（F = 7.47，P < 0.001；F = 4.70，P = 0.005）；给药42 d，与对照组相比，实验组Ⅰ型胶原蛋白表达和Ⅰ/Ⅲ型胶原蛋白比值明显下降（t = 3.04，P = 0.007；t = 2.35，P = 0.030） 。结论 多磺酸黏多糖乳膏局部应用可有效降低瘢痕厚度和抑制胶原纤维增生以及Ⅰ型胶原蛋白表达，预防和抑制瘢痕增生。

关键词: 瘢痕, 模型, 动物, 葡糖氨基聚糖类, 纤维胶原类, 胶原, 多磺酸黏多糖, 增生

Abstract: 【Abstract】 Objective To investigate the inhibitory effect and mechanisms of action of mucopolysaccharide polysulfate cream on hypertrophic scar formation. Methods Circular full-thickness wounds with a diameter of 6 mm were established in both ears of 16 New Zealand white rabbits to establish a rabbit ear model of hypertrophic scar. There were 3 scar wounds in each rabbit ear. About 14 days after the operation, scar wounds on the left ear were topically treated with mucopolysaccharide polysulfate cream, and served as the experimental group; scar wounds on the right ear were topically treated with the cream vehicle, and served as vehicle control group. The dosage of topical agents for one rabbit ear was approximately 0.4 g, which were given twice a day for 6 consecutive weeks. Scar tissues were collected and subjected to hematoxylin and eosin （HE） staining, Masson staining and immunohistochemical study on days 0, 14 and 42, that is, 14, 28 and 56 after operation respectively, so as to evaluate histopathological scores, measure the scar thickness and collagen fiber density, and determine the expression of type Ⅰ and Ⅲ collagen and the ratio of type Ⅰ/Ⅲ collagen. The t test and one-way analysis of variance were used to compare the indices between groups. Results Compared with pretreatment histopathological manifestations, HE staining showed extensive extracellular matrix deposition, inflammatory cell infiltration and local hyperemia in the control group after 42-day treatment, but no obvious changes in the experimental group. The pathological scores of scar tissues on the rabbit ears significantly increased over time in the control group （days 0, 14 and 42: 4.16 ± 1.61, 6.50 ± 1.46, 6.53 ± 1.34, respectively; F = 13.69, P = 0.001）, while there was no significant change in the experimental group （days 0, 14 and 42: 4.65 ± 1.52, 5.13 ± 1.83, 5.38 ± 1.60, respectively; F = 0.78, P > 0.05）. Masson staining showed extremely high content of collagen fibers dyed dark blue in the control group on day 42, but there was a decrease in the content of collagen fibers in the experimental group; with the increase in treatment duration, the thickness of scar tissues significantly increased in the control group compared with that before treatment （F = 5.64, P = 0.007）, while there was no significant change in the experimental group （F = 1.48, P > 0.05）. Immunohistochemical study revealed no significant change in the expression of type Ⅲ collagen in either the experimental group or the control group at any of the above time points compared with that on day 0 （F = 0.22, 0.92, respectively, both P > 0.05）, but the expression of type Ⅰ collagen and the ratio of type Ⅰ/Ⅲ collagen significantly increased in the control group （F = 7.47, P < 0.001; F = 4.70, P = 0.005, respectively）. On day 42, the expression of type Ⅰ collagen and the ratio of type Ⅰ/Ⅲ collagen significantly decreased in the experimental group compared with the control group （t = 3.04, P = 0.007; t = 2.35, P = 0.030, respectively）. Conclusion Topical mucopolysaccharide polysulfate cream is effective in preventing and inhibiting scar hypertrophy by reducing the scar thickness and inhibiting the collagen fiber hyperplasia and type I collagen expression.

Key words: Cicatrix, Models, animal, Lycosaminoglycans, Fibrillar collagens, Collagen, Mucopolysaccharide polysulfate, Hyperplasia