目的·研究柴胡皂苷A（saikosaponin A，SSA）对小鼠髓源性抑制细胞（myeloid-derived suppressor cells，MDSCs）分化、凋亡、免疫抑制功能的调控作用，并探讨其分子机制。方法·用重组小鼠粒细胞-巨噬细胞集落刺激因子（granulocyte-macrophage colony-stimulating factor，GM-CSF）诱导小鼠骨髓细胞（bone marrow cells，BMCs）分化为MDSCs，或磁珠分选荷瘤小鼠MDSCs。以不同浓度（0、2.5、5.0 mg/L）的SSA处理MDSCs后，采用流式细胞术（flow cytometry，FCM）检测MDSCs的分化、凋亡情况，以及肝X受体α（liver X receptor α，LXRα）、精氨酸代谢酶1（arginase-1，Arg-1）、活性氧（reactive oxygen species，ROS）的表达水平，同时检测MDSCs对T细胞增殖功能的影响，以及对核因子κB（nuclear factor κB，NF-κB）、信号转导及转录激活蛋白（signal transducer and activator of transcription 1，STAT1）信号通路的影响。利用实时荧光定量PCR（quantitative real-time PCR，qPCR）检测LXRα和Arg-1的mRNA水平。通过灌胃或腹腔注射给予小鼠SSA，给药结束后处死小鼠，测定其体质量、脾脏，计算脾指数。FCM检测小鼠脾脏内各免疫细胞的比例。结果·SSA可上调MDSCs的LXRα表达水平，减少M-MDSCs的分化，诱导MDSCs凋亡，降低MDSCs的Arg-1和ROS的表达水平，减轻MDSCs对T细胞增殖的抑制作用。SSA可抑制MDSCs中的NF-κB和STAT1的磷酸化水平。经SSA灌胃和腹腔注射处理的小鼠，其体质量以及脾指数均无明显变化。且这2种给药方式均可降低小鼠体内MDSCs及其亚群M-MDSCs的比例，但对其他免疫细胞有不同程度的调控作用。结论·SSA可调控MDSCs的分化、凋亡，并抑制其免疫抑制功能，这可能与SSA上调MDSCs的LXRα表达、抑制NF-κB和STAT1信号通路相关。SSA可通过LXRα逆转MDSCs的免疫抑制功能。

Objective ·To study the regulatory effect of saikosaponin A (SSA) on the differentiation, apoptosis, and immunosuppressive function of myeloid-derived suppressor cells (MDSCs) in mice, and to explore their molecular mechanism. Methods ·Recombinant mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) was used to induce the differentiation of mouse bone marrow cells (BMCs) into MDSCs, or magnetic beads were used to sort MDSCs from tumor-bearing mice. After treating MDSCs with different concentrations (0, 2.5, 5.0 mg/L), flow cytometry (FCM) was used to detect the differentiation and apoptosis of MDSCs, as well as the expression levels of liver X receptor α (LXRα), arginase-1 (Arg-1), and reactive oxygen species (ROS). At the same time, the effects of MDSCs on the proliferation function of T cells, and the effects on the nuclear factor κB (NF-κB), and signal transducer and activator of transcription 1 (STAT1) signaling pathways were also detected. The mRNA levels of LXRα and Arg-1 were detected by quantitative real-time PCR (qPCR). Mice were given SSA by gavage (ig) or intraperitoneal injection (ip), and the mice were sacrificed after administration; and body mass, spleen weight, and spleen index were calculated. FCM was used to detect the proportion of immune cells in the spleen of mice. Results ·SSA could up-regulate the expression level of LXRα in MDSCs, reduce the differentiation of M-MDSCs, induce apoptosis of MDSCs, reduce the expression levels of Arg-1 and ROS in MDSCs, and reduce the inhibitory effect of MDSCs on T cell proliferation. SSA inhibited the phosphorylation levels of NF-κB and STAT1 in MDSCs. The mice treated with SSA by gavage or intraperitoneal injection showed no significant changes in body weight and spleen index. Both modes of administration can reduce the proportion of MDSCs and their subset M-MDSCs in mice, but had different degrees of regulatory effects on other immune cells. Conclusion ·SSA could regulate the differentiation and apoptosis of MDSCs, and inhibit their immunosuppressive function, which may be associated with the up-regulation of LXRα expression, and down-regulation of the NF-κB and STAT1 signaling pathways in MDSCs.