摘要
目的探究芹菜素对雄激素性脱毛(androgenetic alopecia,AGA)小鼠的治疗作用及机制。方法将24只C57BL/6小鼠随机分为空白对照组、模型组、阳性对照组和芹菜素组。建立AGA小鼠模型,空白对照组和模型组小鼠背部涂抹1,2-丙二醇溶液,药物治疗组分别涂抹米诺地尔和芹菜素。观察实验期间小鼠皮毛生长情况,比较新生皮毛长度及质量;利用苏木精-伊红(hematoxylin-eosin,HE)染色观察小鼠毛囊状态及数量;通过蛋白质免疫印迹法(Western blot,WB)检测小鼠皮肤组织中Wnt/β-连环蛋白(Wnt/β-catenin)信号通路关键蛋白及细胞凋亡相关蛋白水平;通过皮肤组织免疫荧光染色检测β-catenin及核因子Ki-67(nuclear protein Ki-67)蛋白表达;使用分子对接软件对芹菜素及预测靶点进行对接分析。结果与模型组相比,芹菜素显著促进AGA模型小鼠皮毛新生,增加毛囊数量,促进毛囊由休止期向生长期转变。WB结果显示,芹菜素显著抑制Axis抑制蛋白1(axis inhibition protein 1,Axin1)、半胱天冬氨酸蛋白酶-3(cysteine-aspartic protease-3,Caspase-3)、Bcl-2相关X蛋白(Bcl-2-associated X protein,Bax)表达,促进B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)、β-catenin及磷酸化糖原合成酶激酶3β(phospho-glycogen synthase kinase 3β,p-GSK3β)/GSK3β蛋白表达,且显著增加小鼠皮肤Ki-67蛋白水平。此外,分子对接结果显示,β-catenin、GSK3β与芹菜素结合性良好。结论芹菜素具有促进AGA模型小鼠皮毛生长的作用,其作用机制可能与抑制毛囊细胞凋亡和激活Wnt/β-catenin信号通路相关。
OBJECTIVE To investigate the therapeutical effect and mechanisms of apigenin on androgenetic alopecia(AGA)in mice.METHODS Mice were divided into four groups:a blank control group,a model group,a positive control group,and an apigenin group.Based on the establishment of an AGA model,both the blank control group and the model group received 1,2-propanediol solution,while the treatment groups were administered minoxidil and apigenin,respectively.Hair growth was observed,and the length and weight of new hair were measured.Hematoxylin-eosin(HE)staining was used to assess follicle growth status and count.Western blotting(WB)was performed to detect the key proteins in Wnt/β-catenin signaling pathway and apoptosis associated proteins.Immunof luorescence staining was used to examineβ-catenin and nuclear protein Ki-67 expressions in skin tissues.Apigenin and its predicted targets were analyzed by virtual molecular docking.RESULTS Compared with the model group,apigenin significantly accelerated hair regeneration in AGA model mice,increased the length and weight of new hair,and elevated the number of hair follicles,promoting the transition from the telogen to the anagen phase.Mechanistic studies indicated that apigenin inhibited cell apoptosis and activated the Wnt/β-catenin signaling pathway,suppressed Axin1,caspase-3,and Bax protein expressions,promoted Bcl-2,β-catenin,and p-GSK3β/GSK3βprotein expressions,increased Ki-67 positive expression in the skin,and enhanced the proliferation and differentiation of hair follicle cells.The molecular docking results showed thatβ-catenin and GSK3βwere well bound to apigenin.CONCLUSION Apigenin promotes hair growth in AGA model mice,possibly through inhibiting cell apoptosis and activating the Wnt/β-catenin signaling pathway.
作者
王子怡
高瑞阳
岳备
艾方彬
刘东徽
张蓓蓓
窦薇
WANG Ziyi;GAO Ruiyang;YUE Bei;AI Fangbin;LIU Donghui;ZHANG Beibei;DOU Wei(Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《中国药学杂志》
北大核心
2025年第12期1255-1261,共7页
Chinese Pharmaceutical Journal
基金
国家自然科学基金项目资助(82274329)。
