目的 研究補骨脂酚對氧糖剝奪/復糖復氧（OGD/R）誘導人源性神經(jīng)母細胞瘤細胞（SH-SY5Y）損傷的影響。方法 MTT法檢測補骨脂酚（5、10、20、40、80 μmol·L⁻¹）對SH-SY5Y細胞活性的影響。將SH-SY5Y細胞分為對照組、模型組、補骨脂酚（5、10、20 μmol·L⁻¹）組、補骨脂酚（20 μmol·L⁻¹）＋ML385（2 μmol·L⁻¹，Nrf2抑制劑）組、補骨脂酚（20 μmol·L⁻¹）＋LY294002[5 μmol·L⁻¹，磷脂酰肌醇3-激酶（PI3K）抑制劑]組。MTT法檢測SH-SY5Y細胞活力，倒置顯微鏡觀察各組SH-SY5Y細胞形態(tài)，試劑盒法檢測細胞上清超氧化物歧化酶（SOD）、過氧化氫酶（CAT）活性，實時熒光定量PCR（qRT-PCR）法和Western blotting法測定磷脂酰肌醇3-激酶（PI3K）、絲氨酸/蘇氨酸激酶B（Akt）、核因子E2相關因子2（Nrf2）、血紅素加氧酶1（HO-1）mRNA和蛋白水平。結果 補骨脂酚對正常SH-SY5Y細胞存活率無影響。與對照組比較，模型組細胞存活率顯著下降（P＜0.01），細胞個數(shù)明顯減少，部分細胞裂解成碎片，部分細胞死亡；SOD、CAT活性顯著降低（P＜0.01），PI3K/Akt/Nrf2/HO-1 mRNA及蛋白水平顯著下調(diào)（P＜0.05、0.01、0.001）。與模型組比較，補骨脂酚顯著增加細胞存活率（P＜0.01），明顯增加細胞個數(shù)，顯著上調(diào)SOD、CAT活性（P＜0.05、0.01），顯著上調(diào)PI3K/Akt/Nrf2/HO-1 mRNA及蛋白水平（P＜0.05、0.01、0.001）。與補骨脂酚（20 μmol·L⁻¹）組比較，補骨脂酚＋ML385可逆轉補骨脂酚對HO-1 mRNA及蛋白的上調(diào)作用（P＜0.05、0.01），補骨脂酚＋LY294002可逆轉補骨脂酚對Nrf2、HO-1 mRNA及蛋白水平的上調(diào)作用（P＜0.05、0.01）。結論 補骨脂酚可顯著改善OGD/R誘導的SH-SY5Y細胞損傷，且機制可能是通過激活PI3K/Akt進而上調(diào)Nrf2/HO-1抑制氧化應激改善神經(jīng)損傷。

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.

安徽省高等學?？茖W研究項目（自然科學類）重點項目（2022AH050524，2023AH050866）;安徽中醫(yī)藥大學第二附屬醫(yī)院“杏林英才”培育計劃項目（2023-0500-48-41，2023-0500-48-46）;安徽省高校優(yōu)秀青年教師項目（YQYB2024030）