黄芪皂苷抑制PHD3酶介导的HIF-1α/NF-κB信号途径调节骨髓巨噬细胞极化改善骨髓抑制微环境的作用及机制研究

气机学说是经典中医理论之一，黄芪则是最广泛使用的补气中药。骨髓微环境在调节免疫、维持机体内环境稳定的过程中起关键作用，但黄芪如何调控骨髓微环境，发挥免疫调节作用的相关机制不清楚。我们前期工作发现黄芪皂苷可显著改善被抑制的骨髓造血微环境，可调节缺氧巨噬细胞活性及调控HIF-1α/NF-κB信号通路共同限速酶PHD3的表达。据此我们提出假设，黄芪皂苷可通过调节PHD3酶介导的HIF-1α/NF-κB信号途径影响骨髓巨噬细胞表型极化，进而改善骨髓抑制微环境。我们将以CoCl2缺氧骨髓巨噬细胞和沉默PHD3基因小鼠为研究对象，以免疫细胞生物学、基因沉默等手段对黄芪皂苷、骨髓巨噬细胞以及PHD3酶的内在相互作用机制进行深入分析，探索黄芪皂苷改善骨髓抑制微环境的内在调控机制。本研究将对揭示黄芪皂苷免疫调节分子机制有重要意义，为深层次阐释黄芪补气内涵提供研究思路，也为黄芪的临床应用提供科学依据。

Qi is one of classic traditional Chinese medical theory and Astragalus membranaceus (AM) is the most widely used traditional Chinese medicine for replenishing Qi. Bone marrow microenvironment plays a key role in regulating immune system and maintaining the stability of internal environment, but the mechanism of AM how to regulate the bone marrow microenvironment and play the role of immune regulation is not clear. Our previous work found that astragalosides (AGs) could significantly improve the suppressed bone marrow microenvironment and regulate the activity of macrophages under hypoxia environment. Besides, AGs aslo could regulate the expression of enzyme PHD3, the common rate-limiting enzyme of HIF-1α/NF-κB. So, we hypothesized that AGs could regulate the polarization of bone marrow macrophages by inhibiting HIF-1α/NF-κB signal pathway mediated by PHD3 enzyme, improving the microenvironment of bone marrow suppression. In this project, CoCl2-induced cells and PHD3-silenced mice models were used as research objects. Besides, immune cellular biology and gene silencing research techniques were used to explore the internal interaction mechanism among AGs, bone marrow macrophage and PHD3, aiming to explore the internal regulatory mechanism of AGs in improving the microenvironment of myelosuppression. This study will be of great significance to reveal the specific molecular mechanism of immune regulation of AGs, provide research ideas for in-depth interpretation of the connotation of replenishing qi of AM, and provide scientific basis for clinical application of AM.