目的 基于铁死亡途径探究五味子乙素（schisandrin B，Sch B）对肝癌细胞增殖的影响及其作用机制，并通过制备成微乳以增强其抑制肝癌细胞增殖的效果。方法 采用CCK-8法和平板克隆法检测Sch B对人肝癌HepG2、Huh7细胞增殖的影响；通过检测肝癌细胞内线粒体形态的变化、Fe²⁺及氧化相关指标的含量、铁死亡过程相关因子表达，来评估Sch B对肝癌细胞内Fe²⁺积累、脂质过氧化程度和铁死亡信号通路的影响。通过伪三元相图和Box-Behnken响应面法筛选基于D-α-生育酚聚乙二醇琥珀酸酯的微乳（D-α-tocopheryl polyethylene glycol succinate-based micromulsion，T-ME）处方，对五味子乙素微乳（Sch B-T-ME）的理化指标进行测定和表征。通过CCK-8法比较Sch B-T-ME与游离Sch B抑制肝癌细胞增殖的效果。结果 Sch B可呈剂量相关性地抑制肝癌细胞增殖。Sch B通过下调谷胱甘肽过氧化物酶4（glutathione peroxidase 4，GPX4）和胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11（solute carrier family 7 member 11，SLC7A11）以及上调酰基辅酶A合成酶长链家族成员4（acyl-CoA synthetase long chain family member 4，ACSL4），导致肝癌细胞抗氧化系统失调，促进脂质过氧化，从而引起肝癌细胞死亡。成功制备了Sch B-T-ME，其平均粒径为（38.29±1.97）nm，Zeta电位为（−4.73±0.36）mV，聚合物分散性指数（polymer dispersity index，PDI）为0.266±0.011。与游离的Sch B相比，Sch B-T-ME对肝癌细胞增殖的抑制作用明显增强。结论 Sch B能够通过铁死亡途径抑制肝癌细胞增殖，且制备的Sch B-T-ME可明显增强Sch B抑制肝癌细胞增殖的作用。

Objective To investigate the effect and mechanism of schisandrin B (Sch B) on proliferation of hepatocellular carcinoma cells based on ferroptosis pathway, and enhance the inhibition of hepatocellular carcinoma cell proliferation through the preparation of microemulsions.Methods The effects of Sch B on proliferation of HepG2 and Huh7 cells were determined by CCK-8 assay and plate cloning method; The effects of Sch B on Fe²⁺ accumulation, lipid peroxidation and ferroptosis signalling pathway were evaluated by detecting the changes of mitochondrial morphology, levels of Fe²⁺ and oxidation-related indicators, and expressions of factors related to ferroptosis process in hepatocellular carcinoma cells. The formulation of D-α-tocopheryl polyethylene glycol succinate (TPGS)-based microemulsions (T-ME) was investigated by pseudoternary phase diagrams and Box-Behnken response surface methodology. The physicochemical indices of TPGS-based microemulsion of Sch B (Sch B-T-ME) were determined and characterised. The effect of Sch B-T-ME was compared with that of free Sch B in inhibiting the proliferation of hepatocellular carcinoma cells using CCK-8 assay. Results Sch B could inhibit the proliferation of hepatocellular carcinoma cells in a dose-dependent manner. Sch B caused HCC cells death by down-regulating glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and up-regulating acyl-CoA synthetase long chain family member 4 (ACSL4), leading to dysregulation of the antioxidant system in hepatocellular carcinoma cells and promoting lipid peroxidation. Sch B-T-ME was successfully prepared with an average particle size of (38.29 ± 1.97) nm, a Zeta potential of (−4.73 ± 0.36) mV and a polymer dispersity index (PDI) of 0.266 ± 0.011. Compared with free Sch B, the inhibitory effect of Sch B-T-ME on proliferation of hepatocellular carcinoma cells was significantly enhanced. Conclusion Sch B inhibits the proliferation of hepatocellular carcinoma cells through ferroptosis pathway, and the prepared Sch B-T-ME can significantly enhance the inhibitory effect of Sch B on proliferation of hepatocellular carcinoma cells.

R285.5