ⅩⅦ型胶原蛋白对雄激素性脱发模型小鼠毛发生长的作用及机制研究  

Effect and mechanism of type ⅩⅦ collagen on hair growth in mice with androgenetic alopecia

作　　者：程含皛 戚吉妮 许言文 钱锡飞 张菊芳 Cheng Hanxiao;Qi Jini;Xu Yanwen;Qian Xifei;Zhang Jufang(Department of Medical Aesthetics,Hangzhou First People’s Hospital,Westlake University School of Medicine,Hangzhou 310006,China;Department of Plastic Surgery,Huzhou Central Hospital,Fifth School of Clinical Medicine of Zhejiang Chinese Medical University,Huzhou 313000,China;Fourth School of Clinical Medicine of Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]西湖大学医学院附属杭州市第一人民医院医疗美容科,杭州310006 [2]浙江中医药大学第五临床医学院湖州市中心医院整形外科,湖州313000 [3]浙江中医药大学第四临床医学院,杭州310053

出　　处：《中华整形外科杂志》2024年第1期56-68,共13页Chinese Journal of Plastic Surgery

基　　金：杭州市医学重点学科(0020200044);杭州市科技发展计划项目(202204B20)。

摘　　要：目的探讨ⅩⅦ型胶原蛋白(COL17)对雄激素性脱发(AGA)模型小鼠毛发生长的作用及机制。方法将48只C57BL/6J小鼠建立AGA模型(脱去小鼠背部毛发并外涂二氢睾酮溶液), 采用随机数表法分为6组, 每组8只。阴性对照组, 脱毛区注射生理盐水(单点注射0.05 ml, 共5个点);阳性对照组, 脱毛区外用5%米诺地尔酊, 1 ml/d;COL17低、中、高浓度组, 在脱毛区分别注射0.5、1.0、2.0 mg/ml的COL17(单点注射0.05 ml, 共5个点);Ⅲ型胶原蛋白(COL3)、COL17(COL3+COL17)联合高浓度组, 在脱毛区注射2.0 mg/ml的COL3和COL17(单点注射0.05 ml, 共5个点)。共给药21 d, 期间观察记录各组小鼠毛发生长情况;21 d后, 取小鼠脱毛区皮肤及皮下组织制作病理切片行HE染色, 观察毛囊数量及形态变化;取小鼠脱毛区新鲜皮肤组织行总RNA测序分析, 对差异共表达基因进行基因本体论(GO)功能注释、京都基因与基因组百科全书(KEGG)通路分析和基因集富集分析(GSEA)。结果给药21 d后, 与阴性对照组相比, 阳性对照组、COL17高浓度组、COL3+COL17联合高浓度组小鼠背部脱毛面积明显缩小, HE染色显示其毛囊数量也明显增多。Pearson相关性分析、主成分分析及各组间聚类热图显示, COL17高浓度组与阳性对照组基因相关性较高(R2=0.95, P=0.024), 基因表达较为接近, 2组有3 882个差异基因(1 705个上调, 2 177个下调), 而COL3+COL17联合高浓度组与阳性对照组基因相关性最高(R2=0.96, P=0.001), 基因表达最接近, 2组有1 289个差异基因(385个上调, 904个下调);KEGG分析显示, 与阴性对照组相比, 阳性对照组、COL17高浓度组及COL3+COL17联合高浓度组小鼠均上调了与毛发生长相关的Wnt信号通路、细胞黏附分子及hedgehog信号通路;GO富集分析提示COL17高浓度组及COL3+COL17联合高浓度组中皮肤发育、毛发周期循环相关基因上调;GSEA富集分析发现, COL17高浓度组成纤维细胞增殖、白介�Objective To investigate the effect and mechanism of typeⅩⅦcollagen(COL17)on hair growth in mice with androgenetic alopecia(AGA).Methods Forty-eight C57BL/6J mice were used to establish AGA model(the back hair of the mice was removed and dihydrotestosterone solution was applied)and divided into 6 groups of 8 mice each by random number table.Negative control group,injection of saline in the depilated area(single point injection of 0.05 ml,5 points in total);positive control group,topical application of 5%minoxidil tincture in the depilated area,1 ml/d;COL17 low,medium and high concentration groups,injection of 0.5,1.0 and 2.0 mg/ml COL17 in the depilated area respectively(single point injection of 0.05 ml,5 points in total);typeⅢandⅩⅦcollagen(COL3+COL17)combined high concentration group,injection of 2.0 mg/ml COL3 and COL17 in the depilated area(single point injection of 0.05 ml,5 points in total).The total treatment time was 21 days,during which the hair growth of mice in each group was observed and recorded.After 21 days,the skin and subcutaneous tissue in the depilated area of the mice were taken to make pathological sections for HE staining,and the number and morphological changes of hair follicles were observed;fresh skin tissue in the depilated area of the mice was taken for total RNA sequencing analysis,and the differentially co-expressed genes were annotated by gene ontology(GO)functional annotation,Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis and gene set enrichment analysis(GSEA).Results After 21 days of treatment,compared with the negative control group,the depilation area on the back of the mice in the positive control group,COL17 high concentration group,and COL3+COL17 combined high concentration group was significantly reduced,and HE staining showed that the number of hair follicles was also significantly increased.Pearson correlation analysis,principal component analysis and cluster heat map between groups showed that COL17 high concentration group had high gene correlatio

关 键 词：毛发 雄激素性脱发 ⅩⅦ型胶原蛋白 Ⅲ型胶原蛋白 毛发再生 

分 类 号：R758.71[医药卫生—皮肤病学与性病学]