目的 研究桂枝茯苓膠囊（ GZFL）對人子宮肌瘤細(xì)胞增殖的抑制作用，同時結(jié)合代謝組學(xué)技術(shù)探討其作用機(jī)制。方法 人子宮肌瘤細(xì)胞分為對照組、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）組，藥物處理細(xì)胞24 h。MTS法檢測細(xì)胞相對存活率并篩選適宜濃度；流式細(xì)胞術(shù)檢測細(xì)胞凋亡和細(xì)胞周期；酶聯(lián)免疫吸附測定（ ELISA）法檢測人子宮肌瘤細(xì)胞B淋巴細(xì)胞瘤-2（ Bcl-2）、增殖細(xì)胞核抗原（ PCNA）表達(dá)；代謝組學(xué)技術(shù)研究GZFL對人子宮肌瘤細(xì)胞的作用機(jī)制。結(jié)果 與對照組比較，GZFL能顯著抑制人子宮肌瘤細(xì)胞增殖（ P＜0.01、0.001）、誘導(dǎo)其發(fā)生凋亡并阻滯細(xì)胞周期（ P＜0.01、0.001）、且可下調(diào)細(xì)胞中Bcl-2、PCNA（ P＜0.05、0.01）蛋白的表達(dá)，均呈濃度相關(guān)性。與對照組相比，GZFL高劑量組中14種差異代謝物下調(diào)，4種差異代謝物上調(diào)。對差異代謝物進(jìn)行進(jìn)一步通路富集得到15條代謝通路，其中精氨酸和脯氨酸代謝，丙氨酸、天冬氨酸和谷氨酸代謝，色氨酸代謝可能是GZFL作用的主要途徑。結(jié)論 GZFL對人子宮肌瘤細(xì)胞具有顯著的抑制作用，可能與干預(yù)氨基酸的代謝、進(jìn)而影響細(xì)胞的能量供給及代謝相關(guān)。

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

江蘇省基礎(chǔ)研究計(jì)劃自然科學(xué)基金--前沿引領(lǐng)技術(shù)基礎(chǔ)研究專項(xiàng)（BK20232014）