荭草苷对帕金森病小鼠运动障碍和多巴胺能神经元存活的影响及机制研究  

Effects of orientin on motor dysfunction and survival of dopaminergic neurons in mice with Parkinson's disease and its mechanism study

作　　者：唐秀玲 高颖 杨乐 TANG Xiuling;GAO Ying;YANG Le(Department of Pharmacy,Tangdu Hospital,Air Force Medical University,Xi'an 710038,China)

机构地区：[1]空军军医大学唐都医院药剂科,陕西西安710038

出　　处：《空军军医大学学报》2025年第3期349-356,共8页Journal of Air Force Medical University

基　　金：国家自然科学基金青年科学基金(82104158);空军军医大学唐都医院引凤计划人才启动项目(2022YFJH011)。

摘　　要：目的探讨荭草苷对MPTP诱导的帕金森病(PD)的改善作用及相关作用机制。方法分别利用MPTP和MPP^(+)诱导体内(C57BL/6小鼠)和体外(SH-SY5Y细胞)PD模型。采用行为学实验评测小鼠运动能力,免疫组化染色观察小鼠多巴胺能神经元的数量,CCK-8法检测细胞活力,流式细胞术检测细胞凋亡和活性氧;利用相应的试剂盒检测SH-SY5Y细胞中SOD、MDA等氧化应激指标的含量,荧光探针JC-1检测线粒体膜电位;Western blotting检测Akt/Nrf2/HO-1通路蛋白和凋亡相关蛋白的表达。结果与MPTP组相比,荭草苷干预能够改善PD小鼠运动功能障碍和黑质区多巴胺能神经元的丢失(P<0.05)。相较于MPP^(+)模型组,荭草苷组细胞活力升高(P<0.05)、细胞凋亡率降低(P<0.01)、细胞氧化应激水平降低(P<0.05)、细胞线粒体膜电位损伤减轻(P<0.05)、Akt/Nrf2/HO-1通路蛋白水平恢复,凋亡相关蛋白Bax、Caspase 3的表达降低(P<0.05),Bcl-2的表达升高(P<0.01)。结论荭草苷对MPTP诱导的PD有显著的改善作用,能够减轻MPP^(+)/MPTP诱导的多巴胺能神经元的凋亡,其作用机制可能与激活Akt/Nrf2/HO-1通路,抑制氧化应激和减轻线粒体损伤有关。Objective To explore the effect of orientin on MPTP-induced Parkinson's disease(PD)and its related mechanisms.Methods MPTP and MPP^(+)were used to induce PD models in vivo(C57BL/6 mice)and in vitro(SH-SY5Y cells).Behavioral tests were used to evaluate the exercise ability of mice,immunofluorescence staining was used to observe the number of dopaminergic neurons in mice.CCK-8 method was used to detect cell viability,and flow cytometry was used to detect cell apoptosis and reactive oxygen species.The levels of SOD,MDA,and other oxidative stress indicators in SH-SY5Y cells were detected by corresponding kits,and the mitochondrial membrane potential was detected by fluorescent probe JC-1.Western blotting was used to detect the expression of Akt/Nrf2/HO-1 pathway proteins and apoptosis-related proteins.Results Compared with MPTP group,orientin improved motor dysfunction and reduced the loss of substantia nigra dopaminergic neurons in PD mice(P<0.05).Compared with MPP^(+)model group,orientin increased cell viability(P<0.05),decreased apoptosis rate(P<0.01),lowered the oxidative stress level of cells(P<0.05),reduced mitochondrial membrane potential damage(P<0.05),restored the protein level of Akt/Nrf2/HO-1 pathway,decreased the expression of apoptosis-related proteins Bax and Caspase 3(P<0.05),and increased the expression of Bcl-2(P<0.01).Conclusion Orientin has a significant improvement effect on MPTP-induced PD,and mitigate the apoptosis of dopaminergic neurons induced by MPP^(+)/MPTP.The underlying mechanism may be related to activation of Akt/Nrf2/HO-1 pathway,suppression of oxidative stress,and attenuation of mitochondrial damage.

关 键 词：荭草苷 MPP^(+)/MPTP 细胞凋亡 氧化应激 线粒体损伤 

分 类 号：R285.5[医药卫生—中药学]