目的：探究山柰素（Kaempferide，KFD）对全反式维甲酸（all-trans retinoic acid，atRA）诱导的神经管畸形（Neural tube defects，NTDs）细胞模型的保护作用及机制。方法：将PC12细胞分为正常组、模型组、KFD不同浓度组，模型组采用atRA建立NTDs细胞模型，KFD不同浓度组先用atRA处理12h后，再用KFD干预24h，通过CCK-8检测细胞活力、LDH检测细胞毒性，筛选出最佳KFD给药浓度。后将细胞分为正常组、atRA组、KFD最佳浓度组，Western Blot检测PCP通路蛋白Wnt5a、Fzd3、Dvl2、p-Jnk以及凋亡相关蛋白Bcl-2、Bax、Cleaved caspase-3的表达水平，TUNEL染色检测各组细胞凋亡率。结果：CCK-8、LDH结果显示，5μmol/L KFD对atRA诱导的PC12细胞损伤模型细胞活性最好且毒性小（P<0.01）。Western Blot结果显示，与正常组相比，atRA组PCP通路指标Wnt5a、Fzd3、Dvl2、p-Jnk以及促凋亡蛋白Bax、Cleaved caspase-3的表达均明显增加（P<0.05或P<0.01），抗凋亡蛋白Bcl-2的表达明显减少（P<0.01）；与atRA组相比，使用KFD干预后的Wnt5a、Fzd3、Dvl2、p-Jnk、Bax以及Cleaved caspase-3蛋白表达均显著降低（P<0.05或P<0.01），Bcl-2蛋白表达升高（P<0.05）。TUNEL染色结果显示，与正常组相比，atRA组细胞凋亡率明显增高（P＜0.01）；与atRA组相比，KFD组细胞凋亡率显著降低（P＜0.01）。结论：KFD对atRA诱导的NTDs细胞模型有显著抗凋亡作用，其机制可能与抑制平面细胞极性（Planar cell polarity，PCP）信号通路有关。

Objective: To investigate the protective effect and mechanism of kaempferide (KFD) on the neural tube defects (NTDs) cell model induced by all-trans retinoic acid (atRA). Methods: PC12 cells were divided into a normal group, a model group, and various KFD concentration groups. The NTDs cell model was induced by atRA in the model group. For the various KFD concentration groups, cells were first treated with atRA for 12 hours and then intervened with KFD for 24 hours. Cell viability was detected by CCK-8 assay, and cytotoxicity was measured by LDH assay to screen out the optimal administration concentration of KFD. Subsequently, cells were regrouped into a normal group, a atRA group, and a KFD optimal concentration group. Western Blot was used to detect the expression of planar cell polarity (PCP) pathway-related proteins including Wnt5a, Fzd3, Dvl2, and p-Jnk, as well as apoptosis-related proteins including Bcl-2, Bax, and Cleaved caspase-3. TUNEL staining was performed to determine the apoptosis rate of cells in each group. Results: The results of CCK-8 and LDH assays showed that 5 μmol/L KFD exerted the best protective effect on cell viability with low cytotoxicity in the atRA-induced PC12 cell injury model (P<0.01). Western Blot results indicated that compared with the normal group, the expressions of PCP pathway-related indicators (Wnt5a, Fzd3, Dvl2, p-Jnk) and pro-apoptotic proteins (Bax, Cleaved caspase-3) in the atRA group were significantly increased (P<0.05 or P<0.01), while the expression of the anti-apoptotic protein Bcl-2 was significantly decreased (P<0.01). In contrast, compared with the atRA group, the expression levels of Wnt5a, Fzd3, Dvl2, p-Jnk, Bax, and Cleaved caspase-3 were significantly reduced after KFD intervention (P<0.05 or P<0.01), and the expression level of Bcl-2 was increased (P<0.05). TUNEL staining results demonstrated that compared with the normal group, the apoptosis rate of cells in the atRA group was significantly increased (P<0.01); compared with the atRA group, the apoptosis rate of cells in the KFD group was significantly decreased (P<0.01). Conclusion: KFD has a significant anti-apoptotic effect on the atRA-induced NTDs cell model, and its mechanism may be related to the inhibition of the PCP signaling pathway.

国家自然科学基金项目（编号：81703978，82574609）；国家中医药管理局青年岐黄学者培养项目（编号：国中医药人教函〔2022〕256号）