目的 研究补骨脂酚对氧糖剥夺/复糖复氧（OGD/R）诱导人源性神经母细胞瘤细胞（SH-SY5Y）损伤的影响。方法 MTT法检测补骨脂酚（5、10、20、40、80 μmol·L⁻¹）对SH-SY5Y细胞活性的影响。将SH-SY5Y细胞分为对照组、模型组、补骨脂酚（5、10、20 μmol·L⁻¹）组、补骨脂酚（20 μmol·L⁻¹）＋ML385（2 μmol·L⁻¹，Nrf2抑制剂）组、补骨脂酚（20 μmol·L⁻¹）＋LY294002[5 μmol·L⁻¹，磷脂酰肌醇3-激酶（PI3K）抑制剂]组。MTT法检测SH-SY5Y细胞活力，倒置显微镜观察各组SH-SY5Y细胞形态，试剂盒法检测细胞上清超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性，实时荧光定量PCR（qRT-PCR）法和Western blotting法测定磷脂酰肌醇3-激酶（PI3K）、丝氨酸/苏氨酸激酶B（Akt）、核因子E2相关因子2（Nrf2）、血红素加氧酶1（HO-1）mRNA和蛋白水平。结果 补骨脂酚对正常SH-SY5Y细胞存活率无影响。与对照组比较，模型组细胞存活率显著下降（P＜0.01），细胞个数明显减少，部分细胞裂解成碎片，部分细胞死亡；SOD、CAT活性显著降低（P＜0.01），PI3K/Akt/Nrf2/HO-1 mRNA及蛋白水平显著下调（P＜0.05、0.01、0.001）。与模型组比较，补骨脂酚显著增加细胞存活率（P＜0.01），明显增加细胞个数，显著上调SOD、CAT活性（P＜0.05、0.01），显著上调PI3K/Akt/Nrf2/HO-1 mRNA及蛋白水平（P＜0.05、0.01、0.001）。与补骨脂酚（20 μmol·L⁻¹）组比较，补骨脂酚＋ML385可逆转补骨脂酚对HO-1 mRNA及蛋白的上调作用（P＜0.05、0.01），补骨脂酚＋LY294002可逆转补骨脂酚对Nrf2、HO-1 mRNA及蛋白水平的上调作用（P＜0.05、0.01）。结论 补骨脂酚可显著改善OGD/R诱导的SH-SY5Y细胞损伤，且机制可能是通过激活PI3K/Akt进而上调Nrf2/HO-1抑制氧化应激改善神经损伤。

Objective To study the protected effect of bakuchiol on human neuroblastoma cells (SH-SY5Y) injury induced by oxygen glucose deprivation/reoxygenation (OGD/R). Methods The effect of BAK (5, 10, 20, 40, and 80 μmol·L⁻¹) on the viability of SH-SY5Y cells was detected by MTT assay. SH-SY5Y cells were divided into control group, model group, the BAK (5, 10, 20 μmol·L⁻¹) groups, the BAK (20 μmol·L⁻¹) + ML385 (2 μmol·L⁻¹, Nrf2 inhibitor) group, and the BAK (20 μmol·L⁻¹) + LY294002 [5 μmol·L⁻¹, phosphatidylinositol 3-kinase (PI3K) inhibitor] group. The viability of SH-SY5Y cells was detected by MTT assay, the morphology of SH-SY5Y cells in each group was observed by inverted microscope, the activities of superoxide dismutase (SOD) and catalase (CAT) in the cell supernatant were detected by kit method, and the mRNA and protein levels of PI3K, serine/threonine kinase B (Akt), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1) were determined by real-time fluorescence quantitative PCR (qRT-PCR) and Western blotting. Results Bakuchiol had no effect on the survival rate of normal SH-SY5Y cells. Compared with the control group, the cell survival rate in the model group was significantly decreased (P < 0.01), the number of cells was significantly reduced, some cells were lysed into fragments, and some cells died; the activities of SOD and CAT were significantly decreased (P < 0.01), and the mRNA and protein levels of PI3K/Akt/Nrf2/HO-1 were significantly down-regulated (P < 0.05, 0.01, 0.001). Compared with the model group, psoralen significantly increased the cell survival rate (P < 0.01), significantly increased the number of cells, significantly up-regulated the activities of SOD and CAT (P < 0.05, 0.01), and significantly up-regulated the mRNA and protein levels of PI3K/Akt/Nrf2/HO-1 (P < 0.05, 0.01, 0.001). Compared with the BAK (20 μmol·L⁻¹) group, BAK + ML385 could reverse the up-regulation effect of BAK on HO-1 mRNA and protein (P < 0.05, 0.01), and BAK + LY294002 could reverse the up-regulation effect of BAK on Nrf2 and HO-1 mRNA and protein levels (P < 0.05, 0.01). Conclusion Bakuchiol can improve the injury of SH-SY5Y cells induced by OGD/R, and the mechanism may be through the activation of PI3K/AKT, leading to the activation of Nrf2/HO-1 to suppress oxidative stress.

安徽省高等学校科学研究项目（自然科学类）重点项目（2022AH050524，2023AH050866）;安徽中医药大学第二附属医院“杏林英才”培育计划项目（2023-0500-48-41，2023-0500-48-46）;安徽省高校优秀青年教师项目（YQYB2024030）