Article(id=1280817563500253356, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1280817479555462000, articleNumber=null, orderNo=null, doi=10.13343/j.cnki.wsxb.20250967, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1766592000000, receivedDateStr=2025-12-25, revisedDate=null, revisedDateStr=null, acceptedDate=1770134400000, acceptedDateStr=2026-02-04, onlineDate=1783300303578, onlineDateStr=2026-07-06, pubDate=1783094400000, pubDateStr=2026-07-04, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1783300303578, onlineIssueDateStr=2026-07-06, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1783300303578, creator=13701087609, updateTime=1783300303578, updator=13701087609, issue=Issue{id=1280817479555462000, tenantId=1146029695717560320, journalId=1192105938417971205, year='2026', volume='66', issue='7', pageStart='3121', pageEnd='3677', issueExtLink='null', onlineDate='null', pubDate='1783094400000', pubDateStr='2026-07-04', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1783300283564, creator='13701087609', updateTime=1783326087324, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1280925708813832745, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1280817479555462000, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1280925708813832746, tenantId=1146029695717560320, journalId=1192105938417971205, issueId=1280817479555462000, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=3366, endPage=3381, ext={EN=ArticleExt(id=1280817565224112301, articleId=1280817563500253356, tenantId=1146029695717560320, journalId=1192105938417971205, language=EN, title=Effects and mechanistic insights of Lactiplantibacillus plantarum CCFM1352 fermentation metabolites on hair follicle cycling, columnId=1192149543992045670, journalTitle=Acta Microbiologica Sinica, columnName=Research Article, runingTitle=null, highlight=null, articleAbstract=

Objective To address the limitations of current hair-loss treatments, we employed an in vitro human dermal papilla cell (HDPC) model and a telogen C57BL/6 mouse model to study the effects of Lactiplantibacillus plantarum CCFM1352 fermentation metabolites and bacterial preparations on the hair follicle cycle and decipher the associated molecular mechanisms. Methods HDPCs were treated with different concentrations of CCFM1352 fermentation metabolites or bacterial lysates in vitro, and cell viability as well as the expression of molecules related to Wnt/β-catenin signaling, anagen/catagen regulation, and apoptosis was assessed. Telogen C57BL/6 mice were administrated with the fermentation metabolites or heat-killed bacterial cells by gavage for 21 days, and changes in hair coverage, follicular structure, and associated signaling molecules were analyzed. Results CCFM1352 fermentation metabolites at a volume fraction of 10% increased the viability of HDPCs to 135.30%, up-regulated Wnt10b and FGF-7, down-regulated DKK1 and TGF-β1, and increased Bcl-2 and decreased Bax, inducing a favorable change pattern associated with the anagen phase. Continuous gavage of the fermentation metabolites promoted the transition of hair follicles from telogen to anagen, increased the hair coverage to 61.62%, and enhanced hair follicle density, dermal thickness, and β-catenin accumulation and nuclear translocation. However, the regulatory effects of bacterial lysate and heat-killed bacteria were weaker in both models and showed only limited improvements in some indices. Conclusion CCFM1352 fermentation metabolites could modulate Wnt/β-catenin-related molecules and the expression of key factors such as FGF-7, TGF-β1, Bcl-2, and Bax, which favors the transition of hair follicles from telogen to anagen and suggests an important role in promoting hair growth. This study provides experimental evidence for the application of bioactive metabolites from probiotics in the field of hair health.

, authors=Zhe WANG, Xin TANG, Bingyong MAO, Qiuxiang ZHANG, Jianxin ZHAO, Wei CHEN, Shumao CUI, authorsList=Zhe WANG, Xin TANG, Bingyong MAO, Qiuxiang ZHANG, Jianxin ZHAO, Wei CHEN, Shumao CUI, authorCompany=null, correspAuthors=Shumao CUI, authorNote=null, correspAuthorsNote=
E-mail:
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目的 针对脱发治疗维持性差、长期用药受限等问题,本研究利用体外人真皮乳头细胞(human dermal papilla cells, HDPCs)模型和休止期C57BL/6小鼠模型,研究植物乳植杆菌(Lactiplantibacillus plantarum) CCFM1352发酵代谢产物及菌体组分对毛囊周期的调控作用及相关机制。 方法 体外以不同浓度的CCFM1352发酵代谢产物或菌体裂解物处理HDPCs,检测细胞活力及Wnt/β-catenin、生长期与退行期转换、细胞凋亡相关分子的表达水平;体内于休止期C57BL/6小鼠连续口服发酵代谢产物或灭活菌体21 d,评估毛发覆盖率、毛囊形态结构及相关信号分子的变化。 结果 体积分数为10%的CCFM1352发酵代谢产物可将HDPCs活力提升至135.30%,并上调Wnt10b、FGF-7表达,下调DKK1、TGF-β1表达,同时伴随Bcl-2上调与Bax下调,整体呈现有利于毛囊生长期的分子信号变化。体内实验表明,连续口服CCFM1352发酵代谢产物可促进毛囊由休止期向生长期转变,毛发覆盖率提高至61.62%,毛囊密度和真皮厚度显著增加,同时增强β-catenin积累及核转位。相比之下,菌体组分在体内外模型中的调控作用整体较弱,仅在部分指标上表现出有限改善。 结论 CCFM1352发酵代谢产物可通过调节Wnt/β-catenin信号通路相关分子,以及FGF-7、TGF-β1、Bcl-2、Bax等关键因子的表达促进毛囊由休止期向生长期转变,在毛发健康维护方面具有潜在应用价值。本研究为益生菌来源生物活性代谢产物在毛发健康领域的开发利用提供了实验依据。

, authors=王哲, 唐鑫, 毛丙永, 张秋香, 赵建新, 陈卫, 崔树茂, authorsList=王哲, 唐鑫, 毛丙永, 张秋香, 赵建新, 陈卫, 崔树茂, authorCompany=null, correspAuthors=崔树茂, authorNote=

作者贡献声明

王哲:实验操作、数据收集与分析、初稿撰写、论文修改;唐鑫:实验指导、审阅、论文修改;毛丙永:细胞实验方案指导、审阅;张秋香:动物实验方案指导、审阅;赵建新:研究资源提供、论文修改;陈卫:研究资源提供、研究宏观指导、论文修改;崔树茂:研究构思和设计、审阅、论文修改。

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Bioactive Materials, 2024, 38: 95-108., articleTitle=Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment, refAbstract=null), Reference(id=1280925249491420155, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, doi=null, pmid=null, pmcid=null, year=2024, volume=14, issue=1, pageStart=20, pageEnd=null, url=null, language=null, rfNumber=[35], rfOrder=37, authorNames=Wang WJ, Wang HL, Long YL, Li Z, Li JJ, journalName=Biomolecules, refType=null, unstructuredReference=Wang WJ, Wang HL, Long YL, Li Z, Li JJ. Controlling hair loss by regulating apoptosis in hair follicles: a comprehensive overview[J]. Biomolecules, 2024, 14(1): 20., articleTitle=Controlling hair loss by regulating apoptosis in hair follicles: a comprehensive overview, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1280925236820427662, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, xref=null, ext=[AuthorCompanyExt(id=1280925236833010575, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, companyId=1280925236820427662, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China), AuthorCompanyExt(id=1280925236841399184, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, companyId=1280925236820427662, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=江南大学 食品学院,江苏 无锡)])], figs=[ArticleFig(id=1280925240859542460, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Figure 1, caption=Effects of different treatments on HDPCs viability for 24 h. A: sMRS; B: CCFM1352-F; C: CCFM1352-L. *P<0.05, **P<0.01, ***P<0.001 vs. the 0 concentration control., figureFileSmall=pOEGkeQVwGLPq83dYJSpLQ==, figureFileBig=xg8lwZh/c0cmFIWGVYFJ6Q==, tableContent=null), ArticleFig(id=1280925240930845629, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=图1, caption=不同处理24 hHDPCs活力的影响, figureFileSmall=pOEGkeQVwGLPq83dYJSpLQ==, figureFileBig=xg8lwZh/c0cmFIWGVYFJ6Q==, tableContent=null), ArticleFig(id=1280925241035703230, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Figure 2, caption=Effects of different treatments on key molecules of the Wnt/β-catenin signaling pathway in HDPCs. A: Relative mRNA expression of β-catenin; B: Protein level of Wnt10b; C: Protein level of DKK1. *P<0.05, **P<0.01, ***P<0.001 vs. the Control group., figureFileSmall=/Pw5/Px1xy8K7AY4eSBjfA==, figureFileBig=NmCCIfLkAgbmKbmO8x/cvA==, tableContent=null), ArticleFig(id=1280925241119589311, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=图2, caption=不同处理对HDPCsWnt/β-catenin信号通路关键分子的影响, figureFileSmall=/Pw5/Px1xy8K7AY4eSBjfA==, figureFileBig=NmCCIfLkAgbmKbmO8x/cvA==, tableContent=null), ArticleFig(id=1280925241195086784, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Figure 3, caption=Effects of different treatments on FGF-7 and TGF-β1 secretion in HDPCs. A: Protein level of FGF-7; B: Protein level of TGF-β1. *P<0.05, **P<0.01, ***P<0.001 vs. the Control group., figureFileSmall=npgsi0N2gHcsMZ7DNHtLMQ==, figureFileBig=WEUjR2pUX1gc3EAnVzaASw==, tableContent=null), ArticleFig(id=1280925241270584257, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=图3, caption=不同处理对HDPCsFGF-7TGF-β1分泌的影响, figureFileSmall=npgsi0N2gHcsMZ7DNHtLMQ==, figureFileBig=WEUjR2pUX1gc3EAnVzaASw==, tableContent=null), ArticleFig(id=1280925241354470338, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Figure 4, caption=Effects of different treatments on the expression of apoptosis-related genes in HDPCs. A: Relative mRNA expression of Bcl-2; B: Relative mRNA expression of Bax. *P<0.05, **P<0.01, ***P<0.001 vs. the Control group., figureFileSmall=O7CuNYDSNOPH7mnMMoy6Zg==, figureFileBig=UvzydzeEqAZRqUfsXO6pZg==, tableContent=null), ArticleFig(id=1280925241417384899, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=图4, caption=不同处理对HDPCs凋亡相关基因表达的影响, figureFileSmall=O7CuNYDSNOPH7mnMMoy6Zg==, figureFileBig=UvzydzeEqAZRqUfsXO6pZg==, tableContent=null), ArticleFig(id=1280925241484493764, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Figure 5, caption=Effects of different treatments on hair regrowth in telogen C57BL/6 mice. A: Dorsal hair coverage in mice (n=6 per group); B: Hair coverage rate on day 14. **P<0.01, ***P<0.001 vs. the Model group., figureFileSmall=GHKfI+i5J7bAXgKEkLW8dw==, figureFileBig=5a8l30+WFGVwEJLHiQ9sSA==, tableContent=null), ArticleFig(id=1280925241572574149, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=图5, caption=不同处理对休止期C57BL/6小鼠背部毛发生长的影响, figureFileSmall=GHKfI+i5J7bAXgKEkLW8dw==, figureFileBig=5a8l30+WFGVwEJLHiQ9sSA==, tableContent=null), ArticleFig(id=1280925241635488710, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Figure 6, caption=Histological effects of different treatments on hair follicle development in dorsal skin of C57BL/6 mice. A: Longitudinal and cross-sectional H&E staining of skin tissue (scale bar=100 μm); B: Quantification of follicle density in cross-sections (n=3); C: Quantification of dermal thickness in longitudinal sections (n=3). *P<0.05, **P<0.01 vs. the Model group., figureFileSmall=FLlOYmLMPFfiQ5E9hrm2Gg==, figureFileBig=5LB+zwm3EJV8kLdHLtgWcQ==, tableContent=null), ArticleFig(id=1280925241702597575, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=图6, caption=不同处理对C57BL/6小鼠背部皮肤毛囊发育的组织学影响, figureFileSmall=FLlOYmLMPFfiQ5E9hrm2Gg==, figureFileBig=5LB+zwm3EJV8kLdHLtgWcQ==, tableContent=null), ArticleFig(id=1280925241782289352, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Figure 7, caption=Effects of different treatments on the Wnt/β-catenin signaling pathway in dorsal skin of mice. A: Protein levels of β-catenin, Wnt10b, and DKK1 in mouse skin tissue (normalized by BCA) (*P<0.05, **P<0.01, ***P<0.001 vs. the Model group); B: Representative immunofluorescence images of β-catenin in skin tissue (Red indicates β-catenin, and blue indicates DAPI-stained nuclei); C: Subcellular localization of β-catenin in follicle regions (The white box marks the enlarged area showing nuclear translocation)., figureFileSmall=3auDmNq/mgJneKDvHLYGmg==, figureFileBig=E350tbrSbxdaV1BVitZqEg==, tableContent=null), ArticleFig(id=1280925241853592521, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=图7, caption=不同处理对小鼠背部皮肤Wnt/β-catenin信号通路相关蛋白表达的影响, figureFileSmall=3auDmNq/mgJneKDvHLYGmg==, figureFileBig=E350tbrSbxdaV1BVitZqEg==, tableContent=null), ArticleFig(id=1280925241929089994, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Figure 8, caption=Effects of different treatments on FGF-7 and TGF-β1 mRNA expression in mouse skin. A: Relative mRNA expression of FGF-7; B: Relative mRNA expression of TGF-β1. *P<0.05, **P<0.01, ***P<0.001 vs. the Model group., figureFileSmall=YxZSwgq7m/drxMc4llNSpA==, figureFileBig=zELXx/tb/gnj/LL8jDbTQQ==, tableContent=null), ArticleFig(id=1280925242004587467, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=图8, caption=不同处理对小鼠皮肤组织中FGF-7TGF-β1 mRNA表达的影响, figureFileSmall=YxZSwgq7m/drxMc4llNSpA==, figureFileBig=zELXx/tb/gnj/LL8jDbTQQ==, tableContent=null), ArticleFig(id=1280925242080084940, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Figure 9, caption=Effects of different treatments on apoptosis-related protein expression in dorsal mouse skin. A: Protein level of Bcl-2 in mouse skin tissue; B: Protein level of Bax in mouse skin tissue. *P<0.05, **P<0.01, ***P<0.001 vs. the Model group., figureFileSmall=9YqK1GU1I3quv42i7tr4pQ==, figureFileBig=tNRWVgzOHGv1hXONB9CAqA==, tableContent=null), ArticleFig(id=1280925242193331149, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=图9, caption=不同处理对小鼠背部皮肤细胞凋亡相关蛋白水平的影响, figureFileSmall=9YqK1GU1I3quv42i7tr4pQ==, figureFileBig=tNRWVgzOHGv1hXONB9CAqA==, tableContent=null), ArticleFig(id=1280925242273022926, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Table 1, caption=

RT-qPCR primer sequences for cell experiments

, figureFileSmall=null, figureFileBig=null, tableContent=
Primer namesPrimer sequences (5′→3′)
β-catenin

F: GCTCTTGTGCGTACTGTCCTTC

R: TGGTGTCGGCTGGTCAGATG

Bcl-2

F: CGAGTGGGATGCGGGAGATG

R: CGGGATGCGGCTGGATGG

Bax

F: CGGGAGCGGCTGTTGGG

R: ATGGTGAGTGAGGCGGTGAG

GAPDH

F: ACACCCACTCCTCCACCTTTG

R: TCCACCACCCTGTTGCTGTAG

), ArticleFig(id=1280925242377880527, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=表1, caption=

细胞实验RT‐qPCR引物序列

, figureFileSmall=null, figureFileBig=null, tableContent=
Primer namesPrimer sequences (5′→3′)
β-catenin

F: GCTCTTGTGCGTACTGTCCTTC

R: TGGTGTCGGCTGGTCAGATG

Bcl-2

F: CGAGTGGGATGCGGGAGATG

R: CGGGATGCGGCTGGATGG

Bax

F: CGGGAGCGGCTGTTGGG

R: ATGGTGAGTGAGGCGGTGAG

GAPDH

F: ACACCCACTCCTCCACCTTTG

R: TCCACCACCCTGTTGCTGTAG

), ArticleFig(id=1280925242440795088, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=EN, label=Table 2, caption=

RT-qPCR primer sequences for animal experiments

, figureFileSmall=null, figureFileBig=null, tableContent=
Primer namesPrimer sequences (5′→3′)
FGF-7

F: GGCTCGGCGTGCTCTCC

R: CCAGGGCGTAGAGGGTGAC

TGF-β1

F: CTGCCCTCGGACGCTTCG

R: CATGGAAGTGTCGCCTGACAG

GAPDH

F: ACACCCACTCCTCCACCTTTG

R: TCCACCACCCTGTTGCTGTAG

), ArticleFig(id=1280925242495321041, tenantId=1146029695717560320, journalId=1192105938417971205, articleId=1280817563500253356, language=CN, label=表2, caption=

动物实验RT‐qPCR引物序列

, figureFileSmall=null, figureFileBig=null, tableContent=
Primer namesPrimer sequences (5′→3′)
FGF-7

F: GGCTCGGCGTGCTCTCC

R: CCAGGGCGTAGAGGGTGAC

TGF-β1

F: CTGCCCTCGGACGCTTCG

R: CATGGAAGTGTCGCCTGACAG

GAPDH

F: ACACCCACTCCTCCACCTTTG

R: TCCACCACCCTGTTGCTGTAG

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植物乳植杆菌CCFM1352发酵代谢产物对毛囊周期的作用及机制探讨
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王哲 , 唐鑫 , 毛丙永 , 张秋香 , 赵建新 , 陈卫 , 崔树茂
微生物学报 | 研究报告 2026,66(7): 3366-3381
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微生物学报 |研究报告 2026 , 66 (7) : 3366 -3381
植物乳植杆菌CCFM1352发酵代谢产物对毛囊周期的作用及机制探讨
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王哲, 唐鑫, 毛丙永, 张秋香, 赵建新, 陈卫, 崔树茂
作者信息
  • 江南大学 食品学院,江苏 无锡
作者简介:

作者贡献声明

王哲:实验操作、数据收集与分析、初稿撰写、论文修改;唐鑫:实验指导、审阅、论文修改;毛丙永:细胞实验方案指导、审阅;张秋香:动物实验方案指导、审阅;赵建新:研究资源提供、论文修改;陈卫:研究资源提供、研究宏观指导、论文修改;崔树茂:研究构思和设计、审阅、论文修改。

Effects and mechanistic insights of Lactiplantibacillus plantarum CCFM1352 fermentation metabolites on hair follicle cycling
Zhe WANG, Xin TANG, Bingyong MAO, Qiuxiang ZHANG, Jianxin ZHAO, Wei CHEN, Shumao CUI
Affiliations
  • School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
出版时间: 2026-07-04 doi: 10.13343/j.cnki.wsxb.20250967
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目的 针对脱发治疗维持性差、长期用药受限等问题,本研究利用体外人真皮乳头细胞(human dermal papilla cells, HDPCs)模型和休止期C57BL/6小鼠模型,研究植物乳植杆菌(Lactiplantibacillus plantarum) CCFM1352发酵代谢产物及菌体组分对毛囊周期的调控作用及相关机制。 方法 体外以不同浓度的CCFM1352发酵代谢产物或菌体裂解物处理HDPCs,检测细胞活力及Wnt/β-catenin、生长期与退行期转换、细胞凋亡相关分子的表达水平;体内于休止期C57BL/6小鼠连续口服发酵代谢产物或灭活菌体21 d,评估毛发覆盖率、毛囊形态结构及相关信号分子的变化。 结果 体积分数为10%的CCFM1352发酵代谢产物可将HDPCs活力提升至135.30%,并上调Wnt10b、FGF-7表达,下调DKK1、TGF-β1表达,同时伴随Bcl-2上调与Bax下调,整体呈现有利于毛囊生长期的分子信号变化。体内实验表明,连续口服CCFM1352发酵代谢产物可促进毛囊由休止期向生长期转变,毛发覆盖率提高至61.62%,毛囊密度和真皮厚度显著增加,同时增强β-catenin积累及核转位。相比之下,菌体组分在体内外模型中的调控作用整体较弱,仅在部分指标上表现出有限改善。 结论 CCFM1352发酵代谢产物可通过调节Wnt/β-catenin信号通路相关分子,以及FGF-7、TGF-β1、Bcl-2、Bax等关键因子的表达促进毛囊由休止期向生长期转变,在毛发健康维护方面具有潜在应用价值。本研究为益生菌来源生物活性代谢产物在毛发健康领域的开发利用提供了实验依据。

植物乳植杆菌CCFM1352  /  发酵代谢产物  /  毛囊周期  /  Wnt/β-catenin信号通路

Objective To address the limitations of current hair-loss treatments, we employed an in vitro human dermal papilla cell (HDPC) model and a telogen C57BL/6 mouse model to study the effects of Lactiplantibacillus plantarum CCFM1352 fermentation metabolites and bacterial preparations on the hair follicle cycle and decipher the associated molecular mechanisms. Methods HDPCs were treated with different concentrations of CCFM1352 fermentation metabolites or bacterial lysates in vitro, and cell viability as well as the expression of molecules related to Wnt/β-catenin signaling, anagen/catagen regulation, and apoptosis was assessed. Telogen C57BL/6 mice were administrated with the fermentation metabolites or heat-killed bacterial cells by gavage for 21 days, and changes in hair coverage, follicular structure, and associated signaling molecules were analyzed. Results CCFM1352 fermentation metabolites at a volume fraction of 10% increased the viability of HDPCs to 135.30%, up-regulated Wnt10b and FGF-7, down-regulated DKK1 and TGF-β1, and increased Bcl-2 and decreased Bax, inducing a favorable change pattern associated with the anagen phase. Continuous gavage of the fermentation metabolites promoted the transition of hair follicles from telogen to anagen, increased the hair coverage to 61.62%, and enhanced hair follicle density, dermal thickness, and β-catenin accumulation and nuclear translocation. However, the regulatory effects of bacterial lysate and heat-killed bacteria were weaker in both models and showed only limited improvements in some indices. Conclusion CCFM1352 fermentation metabolites could modulate Wnt/β-catenin-related molecules and the expression of key factors such as FGF-7, TGF-β1, Bcl-2, and Bax, which favors the transition of hair follicles from telogen to anagen and suggests an important role in promoting hair growth. This study provides experimental evidence for the application of bioactive metabolites from probiotics in the field of hair health.

Lactiplantibacillus plantarum CCFM1352  /  fermentation metabolites  /  hair follicle cycle  /  Wnt/β-catenin signaling pathway
王哲, 唐鑫, 毛丙永, 张秋香, 赵建新, 陈卫, 崔树茂. 植物乳植杆菌CCFM1352发酵代谢产物对毛囊周期的作用及机制探讨. 微生物学报, 2026 , 66 (7) : 3366 -3381 . DOI: 10.13343/j.cnki.wsxb.20250967
Zhe WANG, Xin TANG, Bingyong MAO, Qiuxiang ZHANG, Jianxin ZHAO, Wei CHEN, Shumao CUI. Effects and mechanistic insights of Lactiplantibacillus plantarum CCFM1352 fermentation metabolites on hair follicle cycling[J]. Acta Microbiologica Sinica, 2026 , 66 (7) : 3366 -3381 . DOI: 10.13343/j.cnki.wsxb.20250967
脱发已成为全球性常见的皮肤健康问题,且呈现低龄化趋势。尽管脱发不直接危及生命,但常引发自卑、焦虑及抑郁等心理负担[1]。临床常见的脱发类型包括雄激素性脱发(androgenetic alopecia, AGA)、斑秃(alopecia areata, AA)与休止期脱发(telogen effluvium, TE)。虽然各型脱发的诱因不同,但其共同病理基础均为毛囊周期紊乱,该过程受毛囊局部微环境及多条信号通路的综合调控。
毛囊是由上皮与间充质相互作用构成的微型器官,其底部的真皮乳头细胞(dermal papilla cells, DPCs)是调控毛囊周期的核心信号中心,可通过分泌多种生长因子调控周围上皮干细胞的增殖与分化,从而维持毛囊生长活性与周期稳态[2-3]。毛囊在生长期、退行期和休止期之间持续往复,其中生长期以细胞快速增殖为特征,退行期以程序性凋亡为主导,休止期则处于相对静止状态[4]
毛囊周期的循环受多条信号通路共同调节,其中Wnt/β-catenin通路在生长期的启动中尤为关键,其激活伴随着β-catenin在细胞核内的积累增加。DPCs产生的Wnt配体(如Wnt10b)可促进细胞增殖与毛囊重建,而Dickkopf相关蛋白1 (dickkopf Wnt signaling pathway inhibitor 1, DKK1)则通过抑制Wnt信号降低β-catenin活性[5-7]。此外,转化生长因子β (transforming growth factor β, TGF-β)等抑制因子通过诱导凋亡促使毛囊进入退行期或休止期[8],而真皮来源的生长因子如成纤维细胞生长因子7 (fibroblast growth factor 7, FGF-7)则通过促进上皮细胞增殖维持毛囊处于生长期[9]。Bcl-2家族包括抗凋亡蛋白B细胞淋巴瘤2 (B cell lymphoma 2, BCL-2)和促凋亡蛋白BCL-2相关X蛋白(BCL-2-associated X protein, BAX),Bcl-2/Bax的表达平衡在毛囊细胞凋亡调控中发挥重要作用,进而影响毛囊周期的走向[10]。上述信号分子的协同变化共同调控毛囊周期的进程。
目前临床常用的脱发治疗药物(如米诺地尔与非那雄胺)虽可在一定程度上改善毛发状况,但存在疗效有限、不良反应相对明显及停药后易出现复发等问题。近年来,益生菌发酵代谢产物及其生物活性成分因成分复杂、作用途径多样而备受关注。已有研究表明,乳酸菌发酵产物可通过影响毛囊周期相关信号通路(包括Wnt/β-catenin、TGF-β等)及增强DPCs生长因子分泌等途径促进毛囊发育与毛发生长[11-13]。然而,其具体调控机制,尤其是对DPCs功能及其相关信号网络的作用仍有待进一步系统阐明。
本研究以植物乳植杆菌(Lactiplantibacillus plantarum) CCFM1352发酵代谢产物与菌体组分为研究对象,探讨其对毛囊周期的调控作用。首先在人真皮乳头细胞(human dermal papilla cells, HDPCs)模型中评估两类组分对毛囊相关信号通路的影响,继而在休止期C57BL/6小鼠模型中验证其体内功效。研究重点聚焦Wnt/β-catenin信号通路,并结合FGF-7、TGF-β1及凋亡相关指标的变化探索CCFM1352发酵代谢产物及菌体组分在毛囊生长期启动中的潜在作用,旨在为益生菌来源活性物质在毛发健康领域的深入研究提供实验依据。
植物乳植杆菌(Lactiplantibacillus plantarum) CCFM1352来源于江南大学食品生物技术保藏中心(江苏无锡)。SPF级雄性C57BL/6小鼠,斯贝福(北京)生物技术有限公司。本研究所有动物实验均获得江南大学动物伦理委员会批准,编号为JN. No. 20250430c1360607[267]。
DMEM培养液,ThermoFisher Scientific公司;胎牛血清、胰酶、青霉素-链霉素,Gibco公司;CCK-8试剂盒、RNA提取试剂盒、反转录试剂盒及RT-qPCR相关试剂盒,南京诺唯赞生物科技股份有限公司;Wnt10b、DKK1、β-catenin、FGF-7和TGF-β1 ELISA试剂盒,上海酶联生物科技有限公司;BCA蛋白浓度测定试剂盒,上海碧云天生物技术股份有限公司;米诺地尔,北京索莱宝科技有限公司;非那雄胺,上海麦克林生化科技股份有限公司;常规试剂与MRS培养基成分,国药集团化学试剂有限公司。
酶标仪,ThermoFisher Scientific公司;实时定量PCR仪,Bio-Rad公司;高速冷冻离心机,Eppendorf公司;冷冻干燥机,宁波新芝生物科技股份有限公司;数字切片扫描仪,3DHISTECH公司。
MRS液体培养基(g/L):无水葡萄糖20.0,牛肉膏10.0,蛋白胨10.0,酵母粉5.0,三水合磷酸氢二钾2.6,无水乙酸钠2.0,柠檬酸氢二铵2.0,七水合硫酸镁0.5,一水合硫酸锰0.25,吐温-80 1.0 mL。sMRS培养基(g/L):葡萄糖8.0,酵母提取物5.0,乙酸钠2.0,磷酸氢二钾2.6。
将植物乳植杆菌CCFM1352接种常规MRS平板上,37 ℃培养48 h后挑取单菌落接种于液体MRS培养基(pH 7.0,121 ℃灭菌20 min),37 ℃恒温培养24 h。待CCFM1352生长至对数期(OD600约为3.5),以2%接种量转接至新鲜液体MRS培养基中活化,连续活化2代,获得种子液。
发酵基质采用成分简化的MRS培养基(sMRS),以尽可能降低培养基成分对后续分析的干扰。将种子液以2%接种量接种至液体sMRS培养基,37 ℃静置培养24 h;随后于4 ℃、8 000×g离心15 min,收集上清液经0.22 μm滤膜除菌,调节pH至7.2-7.4,即得CCFM1352发酵上清液(CCFM1352-F),分装后于-80 ℃保存,用于细胞实验。
取部分发酵上清液冻干,制得CCFM1352发酵产物冻干粉,-20 ℃保存,动物实验前以无菌生理盐水复溶。
发酵液经4 ℃、8 000×g离心15 min,收集菌泥,以无菌水重悬后经高压均质裂解(100 MPa)。裂解液于4 ℃、8 000×g离心10 min去除未破碎固形物,调节pH后进行巴氏杀菌处理(65 ℃, 30 min),经平板培养确认无活菌生长。收集上清即为菌体裂解物(CCFM1352-L),于-80 ℃保存,用于体外细胞实验。
种子液按1.2.1节方法活化后,以2%接种量接种至sMRS,37 ℃静置培养24 h。测定活菌数后,于4 ℃、8 000×g离心20 min收集菌体,以无菌生理盐水洗涤后重悬,随后进行巴氏杀菌(65 ℃, 30 min)灭活,经平板培养验证无活菌检出。灭活菌悬液经冻干制得灭活菌体粉(CCFM1352-HK),于-20 ℃保存,动物实验前以无菌生理盐水复溶。
细胞实验中,sMRS以液体形式按体积分数加入培养基;动物实验中,sMRS对照组按与CCFM1352-F冻干粉相同流程制备,使用前以无菌生理盐水复溶。sMRS对照用于评估培养基成分本身可能产生的影响。
HDPCs采用DMEM完全培养基(含10%胎牛血清和1%青霉素-链霉素的DMEM培养基),于37 ℃、5% CO2条件下培养。细胞生长至约80%融合度时,以0.25%胰酶消化,按1:2比例传代。
将HDPCs以1×104个/孔接种于96孔板,贴壁培养24 h。弃去原培养基,分别加入不同处理:体积分数为5%、10%、15%和20%的CCFM1352-F或CCFM1352-L;阴性对照为等体积分数的无菌sMRS;阳性对照为0.1 μmol/L米诺地尔(Minoxidil);另设空白组和调零孔。每组设3个复孔。处理24 h后,每孔加入10 μL CCK-8溶液,继续孵育2 h,于450 nm处测定吸光度,计算细胞活力。
将对数生长期HDPCs以3×105个/孔接种于6孔板,培养24 h待细胞贴壁后弃去培养基。分别加入10%体积分数的CCFM1352-F、5%体积分数的CCFM1352-L、15%体积分数的无菌sMRS和0.1 μmol/L米诺地尔,每组设3个复孔。处理24 h后收集细胞上清液,采用ELISA试剂盒检测Wnt10b、DKK1、FGF-7和TGF-β1含量。实验独立重复3次。
细胞分组及处理同1.3.3节。培养24 h后弃去上清,以预冷PBS洗涤3次,加入RNA提取试剂盒裂解液裂解并收集细胞。提取总RNA后逆转录为cDNA,采用RT-qPCR检测β-catenin、Bcl-2和Bax的mRNA表达水平,以GAPDH为内参基因,采用2-ΔΔCt法计算相对表达量。引物序列见表1。引物根据NCBI数据库中公布的目标基因mRNA序列设计,由生工生物工程(上海)股份有限公司合成。
选取6周龄SPF级雄性C57BL/6小鼠(n=30),适应性饲养1周后开始实验。用电动剃毛器将背部毛发修剪为约2 cm×3 cm的裸露区域,涂抹脱毛膏1-2 min后,以生理盐水棉球擦拭去除残余毛发。当裸露皮肤呈粉红色且无可见毛囊凸起时判定毛囊已同步进入休止期,即成功建立休止期C57BL/6小鼠模型[14]
皮肤稳定24 h后,将小鼠随机分为5组,每组6只。每日灌胃体积为0.2 mL/只。冻干粉均以无菌生理盐水复溶至指定浓度后使用。模型对照组(Model):灌胃等体积无菌生理盐水;阳性对照组(Finasteride):非那雄胺按10 mg/kg体重灌胃[15];sMRS对照组(sMRS):灌胃与CCFM1352-F组等质量的未接菌sMRS培养基冻干粉复溶液,以排除培养基成分的影响;CCFM1352发酵代谢产物组(CCFM1352-F):每只小鼠每日灌胃的冻干粉量等效于1×1010 CFU CCFM1352在相同条件下发酵所产生的上清代谢物;CCFM1352灭活菌体组(CCFM1352-HK):每只小鼠每日灌胃的冻干粉量等效于1×1010 CFU CCFM1352菌体经灭活处理后所得的菌体量。
于干预第0、7、14、21天拍摄小鼠背部皮肤照片。采用ImageJ软件对第14天图像进行毛发区域分割,计算毛发覆盖率,结果以毛发面积占初始脱毛面积的百分比表示。
第21天处死小鼠,取背侧皮肤组织,以4%多聚甲醛固定,石蜡包埋后切片(厚度4 μm),苏木精-伊红(H&E)染色。每组随机选取3只小鼠(n=3),每只取3个视野测定真皮层厚度并统计单位面积毛囊数量,经ImageJ分析后,毛囊密度以个/mm2表示,3处均值作为该动物数据用于组间比较。
采用免疫荧光染色观察小鼠皮肤组织中β-catenin的表达与定位。石蜡切片经脱蜡、复水后,以柠檬酸缓冲液(pH 6.0)进行抗原修复,3% BSA室温封闭30 min;β-catenin一抗(1:200)于4 ℃孵育过夜,CY3标记二抗(1:300)室温避光孵育50 min,DAPI复染后封片;另设阴性对照(省略一抗)。荧光显微镜在统一曝光条件下采集图像,比较各组间相对荧光强度。
剪取背部皮肤组织30 mg,加入预冷PBS匀浆,于4 ℃、3 000×g离心15 min,取上清液于-80 ℃保存。按照ELISA试剂盒说明书测定β-catenin、Wnt10b、DKK1、Bcl-2和Bax含量,并以BCA试剂盒测定总蛋白浓度进行归一化。
提取皮肤组织总RNA并逆转录为cDNA,采用RT-qPCR检测FGF-7和TGF-β1 mRNA表达水平,以GAPDH为内参基因,采用2-ΔΔCt法计算相对表达量。引物序列见表2,设计及合成方法同细胞实验。
采用GraphPad Prism 10.1.0软件进行统计学分析。组间差异比较采用单因素方差分析(one-way ANOVA),多重比较采用Dunnett’s检验。
采用CCK-8法检测不同浓度CCFM1352发酵上清液(CCFM1352‑F)、菌体裂解物(CCFM1352‑L)及其培养基(sMRS)处理24 h后的细胞活力。如图1所示,CCFM1352-F在10%体积分数时显著提高细胞活力至135.30% (P<0.001),其提升幅度高于sMRS在15%体积分数条件下的促进作用(126.10%, P<0.001)。CCFM1352-L在5%-15%体积分数范围内细胞活力维持在80.00%-85.00%。
真皮乳头细胞活力是毛囊由休止期向生长期转化的重要基础。CCFM1352-F在适宜浓度下显著增强HDPCs活力,且其提升幅度高于sMRS处理组,提示该作用并非完全来源于培养基成分。进一步结合已有研究可见,该活力增强的变化方向与文献报道的HDPCs活力调节趋势一致[16-17]。基于上述结果,选取体积分数为10%的CCFM1352-F、体积分数为5%的CCFM1352-L和体积分数为15%的sMRS用于后续机制研究。所选条件下各处理组细胞活力均高于80.00%,未见明显细胞毒性。
Wnt/β-catenin信号通路在毛囊周期调控中发挥核心作用,其中Wnt10b的激活及DKK1的抑制与毛囊生长启动密切相关[5,18]。基于此,本研究检测了HDPCs中β-catenin mRNA表达及Wnt10b、DKK1蛋白含量以评估Wnt/β-catenin通路的变化。如图2所示,与Control组相比,CCFM1352-F和CCFM1352-L均显著下调β-catenin表达(分别降至0.46和0.44,均P<0.001)。sMRS处理后虽能显著降低DKK1蛋白水平(39.40%, P<0.01),但对Wnt10b蛋白水平和β-catenin mRNA表达无显著影响;相比之下,CCFM1352-F显著提高Wnt10b含量(31.78%, P<0.05)并降低DKK1含量(53.08%, P<0.001)。CCFM1352-L对Wnt10b和DKK1均无显著影响。
上述结果表明,CCFM1352-F通过提高Wnt10b并降低DKK1含量在上游调控层面呈现出有利于Wnt/β-catenin通路活化的变化趋势,该变化方向与毛囊生长期启动相关的信号特征相符。此外,与sMRS组相比,CCFM1352-F在Wnt10b上调和DKK1下调方面呈现出更大的变化趋势。
为评估毛囊生长期与退行期相关信号的变化,检测HDPCs上清液中FGF-7与TGF-β1的蛋白含量。如图3所示,CCFM1352-F显著提高FGF-7含量,较Control组增加14.00% (P<0.01),而sMRS和CCFM1352-L均降低FGF‑7含量。对于TGF-β1,仅Minoxidil组和CCFM1352-F组显著降低其含量,分别下降37.78%和24.81% (均P<0.001)。
FGF-7通常与毛囊生长期的维持及上皮细胞增殖相关,而TGF-β1则多被视为与毛囊退行期诱导相关的抑制性因子,二者含量的变化对毛囊周期的推进具有影响[19]。CCFM1352-F处理在体外模型中同时提高FGF-7并降低TGF-β1,表明在毛囊由休止期向生长期转变过程中,其作用特征体现为促生长信号增强并伴随抑制性信号减弱。sMRS处理未能促进FGF-7分泌,且对TGF-β1的降低作用不明显。
为评估HDPCs凋亡相关变化,检测Bcl-2与Bax的mRNA表达水平。如图4所示,仅Minoxidil组与CCFM1352‑F组显著上调Bcl‑2表达,分别为Control组的1.66倍(P<0.05)和1.84倍(P<0.01),而CCFM1352‑L组未产生显著影响。各处理组均显著抑制Bax表达,其中CCFM1352-F组和CCFM1352-L组分别降至Control组的0.38和0.41 (均P<0.001)。
体外细胞实验中,sMRS处理组在基因水平上虽抑制了Bax表达,但同时也抑制了Bcl-2的表达,表明sMRS处理并不完全有利于细胞存活。CCFM1352-F处理组Bcl-2 mRNA表达显著升高,Bax mRNA表达显著降低,该变化方向与既往关于益生菌来源生物活性成分通过调节Bcl-2/Bax平衡影响真皮乳头细胞功能的报道一致[13],表明CCFM1352-F处理后更有利于细胞存活,有助于HDPCs功能的维持及毛囊生长期的延长。
在休止期C57BL/6小鼠模型中各处理组连续21 d口服干预,每隔7 d记录背部皮肤颜色及毛发覆盖情况。该模型中毛囊进入生长期后背部皮肤由粉红色逐渐转为灰黑色并伴随毛干萌出,因此皮肤颜色及毛发覆盖程度可作为毛囊周期进程的直观指标[20]。非那雄胺为口服阳性对照。研究表明,在C57BL/6小鼠脱毛诱导模型中脱毛后7-14 d对应毛囊由休止期向生长期过渡的阶段,且该时间段对干预刺激更为敏感,常被视为干预响应较为明显的阶段[21-22]。因此,本研究选择第14天作为毛发覆盖率的主要定量分析时间点,用以评估各处理组在毛囊生长期启动中的潜在作用。
图5A所示,脱毛处理后小鼠背部皮肤均呈均一的粉红色,表明模型建立成功。干预7 d后,各组脱毛区域皮肤颜色由粉红向深色转变,表明毛囊已开始向生长期转变。
干预14 d时,Finasteride组和CCFM1352-F组的毛发密度及覆盖程度均较Model组明显增加。毛发覆盖率结果(图5B)显示,Model组毛发覆盖率仅为27.37%,而CCFM1352-F组与Finasteride组分别达到61.62% (P<0.01)和70.52% (P<0.001),CCFM1352-HK组和sMRS组与Model组间未见显著差异。CCFM1352-F组在第14天时毛发覆盖率明显高于Model组,且背部皮肤颜色呈现由粉红向深色转变的趋势;CCFM1352-HK组和sMRS组在毛发覆盖率方面未见显著改善,提示其在整体毛发生长表型上的促进作用相对有限,其组织学层面的变化需结合后续结果进一步分析。
纵切面H&E染色结果显示(图6A),Finasteride组毛囊向真皮深层延伸最为明显;CCFM1352-F组毛囊也出现延伸,但程度低于Finasteride组。Model组和CCFM1352-HK组毛囊整体较短,形态特征与休止期毛囊相似。横切面观察中,CCFM1352-F组和CCFM1352-HK组单位面积内毛囊数量均有所增加,且可见毛囊周围色素沉积。
定量分析结果(图6B6C)显示,Model组平均毛囊密度为(36.75±3.11)个/mm2,CCFM1352-F组显著提高至(48.75±7.27)个/mm2 (P<0.01),与Finasteride组[(48.30±2.98)个/mm2]相当;CCFM1352-HK组同样显著提高至(49.00±9.24)个/mm2 (P<0.01)。纵切面分析中,Model组真皮层厚度为(575.60±61.60) μm,Finasteride组与CCFM1352-F组分别增加至(664.50±59.40) μm (P<0.01)和(645.90±72.57) μm (P<0.05),均显著高于Model组;CCFM1352-HK组与Model组相比未见显著差异。sMRS组在毛囊密度和真皮层厚度方面与Model组相比均无显著差异。
CCFM1352-F组毛囊密度增加并伴随真皮层增厚,其变化方向与毛发覆盖率结果相符。相比之下,CCFM1352-HK组毛囊密度虽同样增加,但真皮层厚度无显著变化。已有研究指出,毛囊密度增加和真皮层增厚常被用于反映毛囊向生长期方向的发育状态[23-24];此外,乳酸菌干预所致的类似组织学改变也有相关报道[25]
为评估Wnt/β-catenin通路相关分子的变化,检测皮肤组织中β-catenin、Wnt10b和DKK1的蛋白水平(图7A)。与Model组相比,CCFM1352-F显著上调β-catenin蛋白水平,提高146.83% (P<0.001),其提升幅度高于Finasteride组(70.04%, P<0.001);并显著下调DKK1蛋白水平,降低32.67% (P<0.05),变化方向与Finasteride组一致。CCFM1352-HK同样可显著提高β-catenin (提高62.16%, P<0.05),并显著降低DKK1 (降低44.80%, P<0.01)。与Model组相比,sMRS组β-catenin蛋白水平同样显著提高(提高108.52%, P<0.001),但其提升幅度低于CCFM1352-F组。此外,上述3组处理均未对Wnt10b蛋白水平产生显著影响。
β-catenin的核转位被认为是Wnt/β-catenin通路活化的关键环节[26]。免疫荧光结果显示(图7B7C),CCFM1352-F组皮肤组织内β-catenin荧光信号增强,在毛囊区域可见较为明确的核内定位;Finasteride组同样表现出类似的核转位现象。与Model组相比,CCFM1352-HK组和sMRS组β-catenin荧光信号强度无明显增强,且未见明显核内积累,主要分布于胞质内。
综合以上数据,CCFM1352-F处理不仅显著提高β-catenin蛋白水平,还伴随更为明确的核内定位变化,整体上更有利于Wnt/β-catenin信号通路的活化。CCFM1352-HK组虽β-catenin蛋白水平有所升高并伴随DKK1降低,但β-catenin的亚细胞定位仍主要停留于胞质,未表现出通路激活所需的核转位特征。sMRS处理后虽能提高β-catenin蛋白水平,但其亚细胞定位与CCFM1352-HK组相似,未能促进β-catenin核转位,表明sMRS对Wnt/β-catenin信号通路的活化作用有限。
FGF-7表达上调与生长期维持相关,而TGF-β1表达下调有利于毛囊由休止期向生长期转化[27-28]。基于此,检测连续干预21 d后皮肤组织FGF-7与TGF-β1的mRNA表达水平(图8)。与Model组相比,CCFM1352-F显著上调FGF-7表达至Model组的1.52倍(P<0.001),并显著下调TGF-β1表达至Model组的0.27倍(P<0.001),表明CCFM1352-F同时促进FGF-7上调并抑制TGF-β1表达,更符合毛囊由休止期向生长期转变过程中促生长信号增强、抑制信号减弱的分子特征。CCFM1352-HK显著上调FGF-7表达至1.43倍(P<0.05),但对TGF-β1表达未产生显著影响,提示CCFM1352-HK在一定程度上促进毛囊进入生长期,但未体现对毛囊退行期相关抑制信号的协同调节。sMRS组未影响FGF-7表达,仅下调TGF-β1表达,其变化特征更偏向于减缓退行期相关信号,不足以支持毛囊由休止期向生长期转变。
毛囊在生长期或由休止期向生长期转变时常伴随细胞凋亡下降与细胞存活能力提升[15]。因此,本研究检测了皮肤组织Bcl-2与Bax蛋白水平以评估不同处理对凋亡相关指标的影响(图9)。
与Model组相比,CCFM1352-F显著上调Bcl-2蛋白水平(提高218.08%,P<0.001),并显著下调Bax蛋白水平(降低49.84%,P<0.05),其变化趋势与Finasteride组一致。CCFM1352-HK对Bcl-2无显著影响,但可显著上调Bax水平(提高47.20%,P<0.05)。与Model组相比,sMRS组仅可显著提高Bcl-2蛋白水平。
在小鼠皮肤组织中,CCFM1352-F处理组显著提高Bcl-2蛋白水平并降低Bax蛋白水平,其变化特征整体上更符合细胞存活状态增强的表达模式,与毛囊由休止期向生长期转变过程中凋亡水平降低的特征一致。sMRS处理虽在Bcl-2蛋白水平上呈现一定提高,但未伴随Bax的显著降低,这种仅针对抗凋亡信号(Bcl-2)的单向调节难以反映细胞凋亡水平的整体下降。
本研究基于HDPCs体外模型和休止期C57BL/6小鼠模型发现,植物乳植杆菌(Lactiplantibacillus plantarum) CCFM1352发酵代谢产物在体内外均呈现有利于毛囊由休止期向生长期转变的变化特征。具体而言,发酵代谢产物能够改善HDPCs活力、调节促生长因子及凋亡相关分子等多项功能指标,整体变化方向与毛囊由休止期向生长期转变的特征一致;菌体裂解物仅在部分指标上表现出一定影响。在体内模型中发酵代谢产物不仅改善毛发覆盖和毛囊结构,还在多项信号指标上呈现有利于生长期的变化趋势;相比之下,灭活菌体的整体作用较弱。
Wnt/β-catenin信号通路在毛囊由休止期进入生长期过程中发挥关键作用[5,29]。本研究中CCFM1352发酵代谢产物在体外呈现Wnt10b升高、DKK1降低的变化趋势;在体内呈现β-catenin升高DKK1降低,并能显著促进β-catenin核转位。上述变化方向与既往文献报道的Wnt/β-catenin通路活化状态下的分子特征基本一致[6],也与益生菌来源成分促进毛囊活化的相关报道相符[25],提示CCFM1352发酵代谢产物更有利于Wnt/β-catenin通路的活化。相比之下,CCFM1352菌体相关组分虽在体内能够提高β-catenin蛋白水平并降低DKK1蛋白水平,但未能促进β-catenin核转位,表明其调控作用主要局限于蛋白表达层面,未体现通路活化所需的下游核定位变化。同样,sMRS对照培养基成分虽在体内提高了β-catenin蛋白水平,但也未能有效促进其核转位,表明sMRS对照的作用特征更多表现为单一指标的变化,难以反映Wnt/β-catenin通路的整体激活状态。
FGF-7的表达通常与毛囊生长期维持相关,而TGF-β1则多被视为与毛囊退行期诱导相关的抑制性因子[30-32]。本研究中,CCFM1352发酵代谢产物在体内外模型中均呈现FGF-7相对上调、TGF-β1相对下调的变化趋势,该变化方向与毛囊处于生长期时相关因子的表达特征一致,也与部分天然来源或发酵产物促进毛囊生长期相关因子表达的报道相符[33],提示CCFM1352发酵代谢产物能同时调控毛囊促生长与抑制性信号。相比之下,菌体相关组分和sMRS对照培养基成分仅能够调控单一指标,即菌体相关组分主要体现在体内FGF-7表达的上调,而sMRS对照培养基成分主要表现为对TGF-β1表达的抑制,二者均未体现毛囊由休止期向生长期转变过程中促生长信号增强与抑制信号减弱的协同调控特征。
Bcl-2和Bax常被作为反映细胞存活与凋亡状态的功能性指标,其表达平衡在毛囊细胞凋亡调控及毛囊周期转换中具有重要意义[34-35]。本研究中,CCFM1352发酵代谢产物在体内外均呈现Bcl-2上调、Bax下调的变化方向,整体上与毛囊生长期相关的细胞存活特征一致。相比之下,菌体相关组分和sMRS对照培养基成分在体内外均未同时表现出Bcl-2上调与Bax下调的变化趋势,表明其在调控毛囊相关细胞存活状态方面的作用相对有限。
综合体内外实验结果,CCFM1352发酵代谢产物在多项与毛囊活化相关的指标上呈现一致的促进作用,提示其在推动毛囊由休止期向生长期转变过程中具有一定应用潜力。需要指出的是,本研究采用的HDPCs体外模型和休止期C57BL/6小鼠模型主要反映毛囊生长期启动的早期阶段,难以完全覆盖雄激素性脱发或炎症性脱发等更复杂的病理情境,未来有必要在更具代表性的疾病模型中进一步验证其适用性。此外,CCFM1352发酵代谢产物的具体活性成分尚未明确,仍需借助代谢组学及活性成分分离等技术阐明其主要活性物质及其作用关联靶点,推动相关机制研究的深入开展。

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doi: 10.13343/j.cnki.wsxb.20250967
  • 接收时间:2025-12-25
  • 首发时间:2026-07-06
  • 出版时间:2026-07-04
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  • 收稿日期:2025-12-25
  • 录用日期:2026-02-04
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    江南大学 食品学院,江苏 无锡

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2种不同金属材料的力学参数

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genus
种数
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Percentage of
total species (%)

Genus
种数
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species
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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