胆红素对神经干细胞活性和增殖的影响研究

doi:10.6040/j.issn.1673-3770.0.2023.071

摘要/Abstract

摘要： 目的探究胆红素对神经干细胞(neural stem cells, NSCs)活性和增殖的影响。方法分离培养小鼠NSCs,加入不同浓度的胆红素,培养2 d后行活/死细胞染色;培养7 d后行神经球形成、Ki-67检测和转录组测序分析以探究胆红素对NSCs活性和增殖的影响。结果 1.71~6.84 μmol/L胆红素对NSCs的活性无影响,13.68 μmol/L胆红素降低了NSCs的活性。0.17~6.84 μmol/L胆红素促进NSCs的增殖,当胆红素的浓度达到13.68 μmol/L时,促进增殖的作用消失。胆红素促进了NSCs的Ki-67表达。转录组结果显示胆红素组184个基因上调表达和100个基因下调表达,差异基因与“细胞群体增殖调节”等生物学过程和PI3K-AKT等信号通路相关。结论高浓度的胆红素对NSCs具有毒性作用,低浓度的胆红素不影响NSCs活性,并促进NSCs增殖。

关键词: 胆红素, 神经干细胞, 增殖, 转录组测序

Abstract: Objective To investigate the effect and mechanism of bilirubin on neural stem cell(NSC)viability and proliferation. Methods Primary mouse NSCs were cultured with different concentrations of bilirubin, and live-dead cell staining was performed after 2 days of culture; neurosphere assay, Ki-67 assay, and transcriptome sequencing were performed after 7 days of culture to investigate the effects of bilirubin on NSC viability and proliferation. Results Approximately 1.71-6.84 μmol/L bilirubin had no effect on NSC viability, while 13.68 μmol/L bilirubin decreased NSC viability. Approximately 0.17-6.84 μmol/L bilirubin promoted NSC proliferation, while this pro-proliferation effect disappeared when the bilirubin concentration reached 13.68 μmol/L. Bilirubin increased Ki-67 expression in NSCs. RNA Seq showed that bilirubin upregulated 184 genes and downregulated 100 genes. Gene Ontology analysis suggested that the differentially expressed genes were mainly related to “regulation of cell population proliferation” and other biological processes. KEGG analysis suggested that the differentially expressed genes were related to several pathways, such as the “PI3K-AKT signaling pathway”. Conclusion High bilirubin concentrations were toxic to NSCs, while low bilirubin concentrations had no effect on NSC viability and promoted NSC proliferation.

Key words: Bilirubin, Neural stem cells, Proliferation, RNA-Seq

中图分类号:

R764.4

吴翠萍,朱一丹,李春燕,殷善开. 胆红素对神经干细胞活性和增殖的影响研究[J]. 山东大学耳鼻喉眼学报, 2024, 38(4): 1-6.

WU Cuiping, ZHU Yidan, LI Chunyan, YIN Shankai. Effect of bilirubin on the viability and proliferation of neural stem cells[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(4): 1-6.

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