实用医学杂志2025,Vol.41Issue(11):1618-1626,9.DOI:10.3969/j.issn.1006-5725.2025.11.003
肿节风总黄酮影响骨髓间充质干细胞及其外泌体促进巨核细胞分化的作用及机制
The effects and mechanism of total flavonoids of Sarcandra glabra in modulating bone marrow mesenchy-mal stem cells and their exosomes to promote megakaryocyte differentiation
摘要
Abstract
Objective To investigate the effects and underlying mechanisms of total flavonoids of sarcandra glabra(TFFSG)on bone marrow mesenchymal stem cells(BMSCs)and their derived exosomes in immune thrombo-cytopenia(ITP),with a focus on promoting megakaryocyte differentiation and maturation.Methods BMSCs induced by rabbit anti-rat platelet serum(APS)were divided into five groups:a blank control group,an ITP-BMSCs model group,and three TFFSG intervention groups with low(1.95 µg/mL),medium(3.90 µg/mL),and high doses(7.80 µg/mL).The apoptosis rates and the expression levels of apoptosis-related proteins-B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(BAX),and Cysteinyl aspartate-specific proteinase-3(Caspase-3)-were assessed.Exosomes were isolated from the blank control group(NC-BMSCs-Exos),the ITP-BMSCs model group(ITP-BMSCs-Exos),and the medium-dose TFFSG group(TFFSG-BMSCs-Exos).Each group's exosomes(5 µg/mL)were co-cultured with megakaryocytic lineage Dami cells for 96 hours.Flow cytometry was employed to evaluate the expression of megakaryocytic differentiation markers(CD41a,CD42b,CD61)and the proportion of polyploid cells(≥4 N)in each group.Western Blot analysis was conducted to examine the expression of p-MEK1/2,MEK1/2,p-ERK1/2,and ERK1/2 across all groups.Results Compared with the ITP-BMSCs model group,the apoptosis rates in all TFFSG intervention groups were significantly reduced(P<0.01).In the medium-and high-dose TFFSG groups,BAX and Caspase-3 expression levels were markedly downregulated,whereas Bcl-2 expression was upregulated(P<0.05,P<0.01).Compared with the ITP-BMSCs-Exos group,the TFFSG-BMSCs-Exos group demonstrated increased expression of CD41a+,CD42b+,and CD61+,a higher proportion of polyploid cells(≥4 N)(P<0.05),as well as elevated ratios of p-MEK1/2 to MEK1/2 and p-ERK1/2 to ERK1/2(P<0.05).Conclusion TFFSG inhibits apopto-sis of ITP-state BMSCs in vitro and promotes megakaryocyte differentiation and polyploidization maturation through BMSC-derived exosomes by activating the MEK1/2-ERK1/2 signaling pathway.关键词
免疫性血小板减少症/骨髓间充质干细胞/外泌体/肿节风总黄酮Key words
immune thrombocytopenia/bone marrow mesenchymal stem cells/exosomes/total flavonoids of Sarcandra glabra引用本文复制引用
刘慧珍,卢晓南,柳歌,蔡关庆,李平安,曾英坚,尚广彬..肿节风总黄酮影响骨髓间充质干细胞及其外泌体促进巨核细胞分化的作用及机制[J].实用医学杂志,2025,41(11):1618-1626,9.基金项目
国家自然科学基金项目(编号:82260798,82460802) (编号:82260798,82460802)
江西省中医药管理局科技计划项目(编号:2024B0451) (编号:2024B0451)
江西中医药大学中西医结合一级学科(编号:江西省双一流学科zxyylxk20220103) (编号:江西省双一流学科zxyylxk20220103)