牛磺酸通过调节毛囊周期及相关信号通路减轻雄性C57BL/6小鼠雄激素性脱发
CSTR:
作者:
作者单位:

1)长治医学院基础医学院,长治 046000;2)山西农业大学动物医学学院,太谷 030801

作者简介:

通讯作者:

中图分类号:

基金项目:

国家自然科学基金(31772690),山西省自然科学基金(201701D121106)和长治医学院博士科研启动基金(BS202308)资助项目。


Taurine Alleviates Androgenetic Alopecia in Male C57BL/6 Mice by Modulating Hair Follicle Cycle and Related Signaling Pathways
Author:
Affiliation:

1)Basic Medicine College, Changzhi Medical College, Changzhi 046000, China;2)College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, China

Fund Project:

This work was supported by grants from The National Natural Science Foundation of China (31772690), the Natural Science Foundation of Shanxi Province (201701D121106), and PhD Research Startup Foundation of Changzhi Medical College (BS202308).

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的 研究牛磺酸对二氢睾酮(DHT)诱导的雄性C57BL/6小鼠雄激素性脱发(AGA)的潜在保护作用及其机制,重点研究毛囊周期调节、细胞增殖/凋亡及相关信号通路。方法 使用雌性C57BL/6小鼠来评估牛磺酸的毛发生长促进潜力。将6周龄雌性C57BL/6小鼠适应性饲养,然后随机分为3组(n=8):对照组(普通饮用水)、牛磺酸组(含1%牛磺酸的饮用水)和米诺地尔组(外用2%米诺地尔,阳性对照组)。将6周龄雄性C57BL/6小鼠适应性饲养,然后随机分为5组 (n=8):对照组(生理盐水)、DHT(模型组,DHT 1 mg/d)、DHT+低剂量牛磺酸(DHT 1 mg/d+牛磺酸2 mg/d)、DHT+高剂量牛磺酸(DHT 1 mg/d +牛磺酸10 mg/d)、DHT+米诺地尔(阳性对照组,DHT 1 mg/d,局部应用2%米诺地尔)。使用剪刀剃去背毛,并在治疗前一天使用脱毛膏去除毛发。毛发再生通过定期拍摄脱毛区域并用四点分级系统(0~3)量化评估。在第14天采集背部皮肤样本,用于组织学分析(苏木精-伊红(HE)染色)、免疫荧光染色(Ki67用于检测毛囊细胞增殖,原位末端转移酶标记法(TUNEL)用于检测毛囊细胞凋亡)、酶联免疫吸附分析(ELISA)(DHT定量)、逆转录-实时定量聚合酶链式反应(RT-qPCR)和蛋白质印迹(Western blot,WB)分析,以评估关键基因和蛋白质(雄激素受体(AR)、转录生长因子(TGF)-β1、TGF-β2、Dickkopf相关蛋白1(DKK1))的表达。结果 在雌性小鼠中,补充牛磺酸能显著加速毛发生长,表现在小鼠皮肤较早从粉红色(毛发休止期)向黑色(毛发生长期)转变,以及毛发生长评分增加,其效果与米诺地尔相当。形态学分析结果显示:牛磺酸显著增加了毛囊数量和真皮厚度。免疫荧光证实,毛发基质中角质细胞增殖增强。在DHT诱导的AGA模型中,DHT显著延长休止期,抑制毛发生长,增加皮肤DHT含量,并诱导毛囊小型化。牛磺酸的治疗,特别是高剂量牛磺酸有效地抵消了这些影响:它促进了毛发由休止期向生长期转变,改善了毛发生长评分。形态学分析结果显示:牛磺酸显著恢复了DHT导致的真皮厚度、毛囊数量、毛球深度和毛囊大小的改变。Ki67和TUNEL分析表明,牛磺酸处理减少了毛囊细胞凋亡并促进了毛囊细胞的增殖。至关重要的是,RT-qPCR和WB分析表明,DHT在mRNA和蛋白质水平上显著上调了小鼠背部皮肤中AR、TGF-β1、TGF-β2和DKK1的表达。牛磺酸的施用显著下调了这些致病因子的表达,使它们更接近对照组的水平。结论 牛磺酸对DHT诱导的雄性C57BL/6小鼠AGA有明显的缓解作用。它的保护作用是通过多方面的机制介导的。a. 促进毛囊周期进展:它加速毛发从休止期向生长期转变,抵消DHT诱导的毛囊休止期延长。b. 调节细胞动力学:它刺激毛囊基质角质细胞的增殖,并减少了DHT诱导的毛囊细胞凋亡。c. 抑制雄激素驱动的致病途径:它下调AGA途径中关键分子的表达,包括AR、细胞因子TGF-β1和TGF-β2,以及Wnt途径抑制剂DKK1。鉴于其良好的安全性和多靶点作用,牛磺酸有望成为治疗AGA的新型候选药物或辅助药物,值得进一步研究其临床潜力和精确的分子机制。这项研究为考虑在脱发治疗策略中补充牛磺酸或局部应用牛磺酸提供了坚实的临床前基础。

    Abstract:

    Objective This study aimed to comprehensively investigate the potential protective effects and underlying mechanisms of taurine against dihydrotestosterone (DHT)-induced androgenetic alopecia (AGA) in male C57BL/6 mice, with a focus on hair follicle cycle modulation, cellular proliferation/apoptosis, and key related signaling pathways.Methods Six-week-old female C57BL/6 mice were initially used to assess the hair growth-promoting potential of taurine. After acclimatization, they were randomly assigned to three groups (n=8): control (regular drinking water), taurine (drinking water containing 1% taurine), and minoxidil (topical 2% minoxidil, positive control). For the AGA study, male C57BL/6 mice were randomly divided into five groups (n=8): control (physiological saline), DHT (model group, 1 mg/d DHT), DHT+low-dose taurine (1 mg/d DHT+2 mg/d taurine), DHT+high-dose taurine (1 mg/d DHT+10 mg/d taurine), and DHT+minoxidil (positive control, 1 mg/d DHT+topical 2% minoxidil). One day before treatment initiation, dorsal hair was shaved with scissors, and residual hair was removed using a depilatory cream. DHT and taurine were administered via daily intraperitoneal injection. Hair regrowth was assessed by photographing the depilated area at regular intervals and quantified using a four-point grading system (0-3). Dorsal skin samples were collected on day 14 for histological analysis (H&E staining), immunofluorescence staining (Ki67 for proliferation, TUNEL for apoptosis), ELISA (DHT quantification), RT-qPCR, and Western blot analysis to evaluate the expression of key genes and proteins (androgen receptor (AR), transforming growth factor (TGF)-β1, TGF-β2, Dickkopf-1 (DKK1)).Results In female mice, taurine supplementation significantly accelerated hair growth, with effects comparable to minoxidil. This was evidenced by an earlier transition from pink (telogen) to black (anagen) skin and increased hair growth scores. Histological analysis showed that taurine increased hair follicle count and dermal thickness. Immunofluorescence confirmed enhanced keratinocyte proliferation in the hair matrix. In the DHT-induced AGA model, DHT significantly extended the telogen phase, inhibited hair growth, increased skin DHT content, and induced hair follicle miniaturization. Taurine treatment, particularly at the high dose, effectively counteracted these effects: it promoted the telogen-to-anagen transition and improved hair growth scores. Histomorphometric analysis showed that taurine significantly restored DHT-induced reductions in dermal thickness, hair follicle count, hair bulb depth, and follicle size. Taurine treatment also reduced apoptosis and promoted the proliferation of hair follicle cells, as demonstrated by Ki67 and TUNEL assays. Crucially, RT-qPCR and Western blot analyses revealed that DHT significantly up-regulated the expression of AR, TGF-β1, TGF-β2, and DKK1 at both mRNA and protein levels in dorsal skin. Taurine administration markedly down-regulated the expression of these pathogenic factors, bringing them closer to the levels observed in the control group.Conclusion Taurine demonstrates significant efficacy in alleviating DHT-induced AGA in male C57BL/6 mice. Its protective effects are mediated through multi-faceted mechanisms. (1) Promoting hair follicle cycle progression: it accelerates the transition from telogen to anagen, counteracting DHT-induced prolongation of the telogen phase. (2) Modulating cellular dynamics: it stimulates the proliferation of hair matrix keratinocytes and reduces DHT-induced apoptosis within hair follicle cells. (3) Suppressing androgen-driven pathogenic pathways: it downregulates the expression of critical molecules in the AGA pathway, including AR, the cytokines TGF-β1 and TGF-β2, and the Wnt pathway inhibitor DKK1. Given its favorable safety profile and multi-targeted action, taurine emerges as a promising novel therapeutic candidate or adjunct for treating AGA. Further investigation into its clinical potential and precise molecular mechanisms is warranted. This study provides a robust preclinical foundation for considering taurine supplementation or topical application in hair loss management strategies.

    参考文献
    相似文献
    引证文献
引用本文

吴晋强,郭果果,张欣婷,刘晋佳,王吉祥,赫晓燕,王海东.牛磺酸通过调节毛囊周期及相关信号通路减轻雄性C57BL/6小鼠雄激素性脱发[J].生物化学与生物物理进展,2025,52(11):2854-2868

复制
相关视频

分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2025-05-29
  • 最后修改日期:2025-10-25
  • 录用日期:2025-09-19
  • 在线发布日期: 2025-09-22
  • 出版日期: 2025-11-28
文章二维码