吉林大学学报（医学版）2025，Vol.51Issue(2)：317-324,8.DOI:10.13481/j.1671-587X.20250205
17β-雌二醇对海马神经干细胞增殖和分化的影响及其机制
Influence of 17β-estradiol in proliferation and differentiation of hippocampal neural stem cells and its mechanism
摘要
Abstract
Objective:To investigate the influence of 17β-estradiol(17β-E2)in the proliferation and differentiation capabilities of primary cultured hippocampal neural stem cells(NSCs),and to clarify its potential mechanism.Methods:The NSCs were isolated from the hippocampal tissue of SD rats within 24 h of birth,and divided into control group and 17β-E2 group.Immunofluorescence method was used to detect the expressions of Nestin and 5-ethynyl-2'-deoxyuridine(EdU)in NSCs in two groups,and the proliferation rates of NSCs were calculated.Western blotting method was used to detect the expression level of Nestin protein.Flow cytometry was used to analyze the percentages of NSCs at different cell cycles.Immunofluorescence method was used to identify the expressions of markers for neurons β Ⅲ-tubulin and astrocyte marker glial fibrillary acidic protein(GFAP)in the NSCs after differentiation,and the relative ratio of neurons to astrocytes was calculated.Western blotting method was used to detect the expression levels of β Ⅲ-tubulin and GFAP proteins as well as phosphatidylinositol 3-kinase(PI3K),protein kinase B(Akt),phosphorylated Akt(p-Akt),glycogen synthase kinase-3 beta(GSK-3β),phosphorylated GSK-3β(p-GSK-3β),and beta-catenin(β-catenin)proteins related to PI3K/Akt/GSK-3β pathway.Results:Immunofluorescence assay revealed positive Nestin expression in NSCs in two groups;compared with control group,the proliferation rate of NSCs in 17β-E2 group was increased(P＜0.01).Compared with control group,the expression level of Nestin protein in the NSCs in 17β-E2 group was increased(P＜0.05),and the percentage of NSCs in S phase was increased(P＜0.01).Compared with control group,the relative ratio of neurons to astrocytes in 17β-E2 group was significantly increased(P＜0.05).After differentiation,compared with control group,the expression level of β Ⅲ-tubulin protein in the NSCs in 17β-E2 group was increased(P＜0.05),and the expression level of GFAP protein was decreased(P＜0.01),while the expression levels of Akt,p-Akt,β-catenin,and p-GSK-3β proteins were increased(P＜0.05 or P＜0.01),and the expression level of GSK-3β protein was decreased(P＜0.05).Conclusion:17β-E2 can promote the proliferation of NSCs and facilitate their differentiation towards neurons,and its mechanism may be related to the PI3K/Akt/GSK-3β signaling pathway.关键词
17β-雌二醇/神经干细胞/细胞增殖/细胞分化/磷脂酰肌醇3-激酶/蛋白激酶B/糖原合成酶激酶3βKey words
17β-estradiol/Neural stem cells/Cell proliferation/Cell differentiation/Phosphatidylinositol 3-kinase/Protein kinase B/Glycogen synthase kinase-3 beta分类
临床医学引用本文复制引用
杨英,赵亮,由涌,许倩,杨振军..17β-雌二醇对海马神经干细胞增殖和分化的影响及其机制[J].吉林大学学报（医学版）,2025,51(2):317-324,8.基金项目
国家自然科学基金项目(81700310) （81700310）
承德医学院高层次人才科研启动基金项目(202108) （202108）
