目的 研究桂枝茯苓胶囊（ GZFL）对人子宫肌瘤细胞增殖的抑制作用，同时结合代谢组学技术探讨其作用机制。方法 人子宫肌瘤细胞分为对照组、GZFL（ 0.4、0.5、0.6、0.7、1.0 mg·mL^-1）和米非司酮（ RU-486，20、25、30、40、90 μmol·L^-1）组，药物处理细胞24 h。MTS法检测细胞相对存活率并筛选适宜浓度；流式细胞术检测细胞凋亡和细胞周期；酶联免疫吸附测定（ ELISA）法检测人子宫肌瘤细胞B淋巴细胞瘤-2（ Bcl-2）、增殖细胞核抗原（ PCNA）表达；代谢组学技术研究GZFL对人子宫肌瘤细胞的作用机制。结果 与对照组比较，GZFL能显著抑制人子宫肌瘤细胞增殖（ P＜0.01、0.001）、诱导其发生凋亡并阻滞细胞周期（ P＜0.01、0.001）、且可下调细胞中Bcl-2、PCNA（ P＜0.05、0.01）蛋白的表达，均呈浓度相关性。与对照组相比，GZFL高剂量组中14种差异代谢物下调，4种差异代谢物上调。对差异代谢物进行进一步通路富集得到15条代谢通路，其中精氨酸和脯氨酸代谢，丙氨酸、天冬氨酸和谷氨酸代谢，色氨酸代谢可能是GZFL作用的主要途径。结论 GZFL对人子宫肌瘤细胞具有显著的抑制作用，可能与干预氨基酸的代谢、进而影响细胞的能量供给及代谢相关。

Objective To investigate the inhibitory effect of Guizhi Fuling Capsule (GZFL) on the proliferation of human uterine leiomyoma cells and to explore its mechanism of action using metabolomics technology. Methods Human uterine fibroid cells were divided into the control group, the GZFL (0.4, 0.5, 0.6, 0.7, 1.0 mg·mL^-1) group and the mifepristone (RU-486, 20, 25, 30, 40, 90 μmol·L^-1) group, and the cells were treated with drugs for 24 h. The relative survival rate of cells was detected by the MTS method and the appropriate concentration was screened. Cell apoptosis and cell cycle were detected by flow cytometry; The expressions of B-lymphoblastoma-2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) in human uterine fibroid cells were detected by ELISA. Metabolomics technology was used to study the mechanism of action of GZFL on human uterine fibroid cells. Results Compared with the control group, GZFL could significantly inhibit the proliferation of human uterine fibroids cells (P < 0.01, 0.001), induce apoptosis and arrest the cell cycle (P < 0.01, 0.001), and down-regulate the expression of Bcl-2 and PCNA proteins in cells (P < 0.05, 0.01), all in a concentration-dependent manner. Compared with the control group, 14 differential metabolites were down-regulated and four differential metabolites were up-regulated in the high-dose GZFL group. Further pathway enrichment of the differential metabolites yielded 15 metabolic pathways, among which arginine and proline metabolism, alanine, aspartate and glutamate metabolism, and tryptophan metabolism might be the main pathways of GZFL action. Conclusion GZFL exhibits a significant inhibitory effect on UMCs, possibly by interfering with amino acid metabolism, thereby affecting the cells' energy supply and metabolic demands.

R285.5

江苏省基础研究计划自然科学基金--前沿引领技术基础研究专项（BK20232014）