基于蛋白质组学研究淫羊藿次苷Ⅱ对巨噬细胞的免疫调控作用

A study on immunoregulatory effects of icariside Ⅱ on macrophages based on proteomics

中文关键词: 巨噬细胞  慢性炎症  淫羊藿次苷Ⅱ  免疫调节  蛋白质组学技术  信号通路

英文关键词: macrophages  chronic inflammation  icariside Ⅱ  immune regulation  proteomics technology  signaling pathway

中文摘要:

      目的 本研究通过蛋白质组学技术探讨淫羊藿次苷Ⅱ(IcarisideⅡ,ICAⅡ)对巨噬细胞极化的调控作用及其分子机制.方法 实验采用RAW264.7小鼠腹腔巨噬细胞,分别通过脂多糖(LPS)或白介素-4(IL-4)诱导其极化为M1型和M2型,并用10 μmol/L的ICAⅡ干预,随后进行非标定量蛋白组学分析(Label-free Quantitative Proteomics,LFQ).结果 本研究表明,在ICA Ⅱ干预M1型巨噬细胞鉴定出809个差异表达蛋白,其中表达上调有443个,下调366个,富集于代谢途径、溶酶体、自噬、氧化磷酸化等信号通路;在ICAⅡ干预M2型巨噬细胞鉴定出654个差异表达蛋白,其中表达上调有324个,下调有330个,富集于脂肪酸代谢、PPAR-γ、VEGF信号通路、氧化磷酸化、铁死亡等通路.结论 ICAⅡ通过调控脂肪酸代谢、PPAR-γ和VEGF信号通路,介导巨噬细胞M1/M2型极化,发挥免疫调节作用.本研究为ICA Ⅱ在控制老龄化疾病的慢性炎症和免疫衰老中的应用提供参考依据.

英文摘要:

      Objective To investigate the immunoregulatory effects of icariside Ⅱ(ICA Ⅱ)on macrophages polariza-tion and its molecular mechanism based on proteomics technology.Methods RAW264.7 mouse peritoneal macrophages were polarized into M1-type[induced by lipopolysaccharide(LPS)]or M2-type[induced by interleukin-4(IL-4)],respectively.Then they were treated with 10 μmol/L ICA Ⅱ.Subsequently,Label-free quantitative proteomics(LFQ)analysis was conduc-ted.Results In M1 macrophages treated with ICA Ⅱ,809 differentially expressed proteins were identified,of which 443 were up-regulated and 366 were down-regulated.They were enriched in signaling pathways such as metabolic pathway,lysosome,autophagy,and oxidative phosphorylation.In M2 macrophages treated with ICA Ⅱ,654 differentially expressed proteins were identified,of which 324 were up-regulated and 330 were down-regulated.They were enriched in fatty acid metabolism,PPAR-γ,VEGF signaling pathway,oxidative phosphorylation,ferroptosis.Conclusion ICA Ⅱ exerts immunomodulatory effects by regulating fatty acid metabolism,PPAR-γ and VEGF signaling pathways and mediating M1/M2 polarization of macrophages.This study provides a reference basis for the application of ICA Ⅱ in controlling chronic inflammation and immunosenescence of age-related diseases.