银杏叶片对多巴胺神经元损伤的保护作用及机制

The neuroprotective effects and mechanism of Ginkgo biloba tablet on dopaminergic neuron damage

目的 探索银杏叶片对MPP^(+)诱发的SH-SY5y细胞损伤的保护作用及对Nrf2/HO-1信号通路的影响。方法 采用MPP^(+)孵育SH-SY5y细胞制备体外帕金森病细胞模型;予以银杏叶片含药血清干预,观察其对多巴胺能神经元损伤的改善作用及对Nrf2、HO-1、ROS水平的影响;采用Nrf2/HO-1信号通路特异性抑制剂干预,探索银杏叶片神经保护作用与Nrf2/HO-1信号通路的关系。结果 (1)银杏叶片含药血清显著减轻了MPP^(+)诱发的SH-SY5y细胞损伤,升高了细胞Nrf2、HO-1的表达水平,抑制了ROS生成(P<0.05);(2)JNK、ERK抑制剂显著减弱了银杏叶片含药血清的细胞保护作用及抗氧化作用(P<0.05);(3)P38抑制剂对银杏叶片含药血清的作用无显著影响(P>0.05)。结论 银杏叶片可有效改善MPP^(+)诱发的SH-SY5y细胞损伤,机制与JNK、ERK途径介导的Nrf2/HO-1信号通路激活有关。

Objective To investigate the protective effect of Ginkgo biloba tablet on MPP~+-induced SH-SY5y cell damage and on the activity of Nrf2/HO-1 signaling pathway.Methods A cell model of Parkinson's disease(PD) was established by MPP~+-stimulation followed by incubation with Ginkgo biloba tablet-containing serum in vitro.The effects of the drug-containing serum on the dopaminergic neuron damage as well as on the levels of Nrf2,HO-1 and ROS were examined.Additionally,specific inhibitors of the Nrf2/HO-1 signaling pathway were used to verify the correlation between the neuroprotective effect and the activity of Nrf2/HO-1 signaling pathway.Results Ginkgo biloba tablet-containing serum markedly attenuated the injury of the SH-SY5y cells induced by MPP~+-stimulation,promoted the expression of Nrf2 and HO-1,and inhibited the ROS production from SH-SY5y cells.However,ERK inhibitor PD98059 and JNK inhibitor SP600125,but not P38 inhibitor SB203580,significantly abolished the neuroprotective effects and anti-oxidative actions of Ginkgo biloba tablet-containing serum in the SH-SY5y cells.Conclusion Ginkgo biloba tablet-containing serum can effectively ameliorate the SH-SY5y cell damage induced by MPP~+-stimulation and the neuroprotective effects in the PD cell model might be associated with the activation of Nrf2/HO-1 signaling through JNK and ERK pathways.