罗汉果苷Ⅴ在帕金森病模型中的神经保护机制研究OA

Siraitia grosvenorii,a characteristic plant of Guangxi,is a precious Chinese medicinal material that can be used both as medicine and food.Mogroside Ⅴ(MⅤ)is a principal bioactive constituent of S.grosvenorii,and possesses potential neuroprotective effects,but the specific mechanism remains unclear.In this study,to establish the Parkinson's disease(PD)primary neurons model,primary cortical neurons were isolated from C57BL/6J fetal mice for 7 days' culture,α-synuclein(α-Syn)preformed fibrils(PFF)were added to the cellular cultural medium.Then,100 μmol·L-1 MⅤ was used to intervene in the PD primary neurons model.Western blot and cellular immunofluorescence analysis were applied to evaluate the effects of MⅤ on the key PD proteins α-Syn,dopamine receptor D1(DRD1)and N-methyl-D-aspartate receptor NR1 subunit(NMDAR1).Furthermore,to clarify the specific mechanism by which MⅤ affects the expression of DRD1,this study established a PD cell model by adding 10 μg·mL-1 α-Syn PFF to the PC12 cell line.In addition,using NMDAR1 plasmid overexpression technology,the interrelationship among α-Syn,DRD1 and NMDAR1 in PC 12 cells was examined.The results were as follows:(1)10 μg·mL-1 α-Syn PFF significantly decreased the expression levels of DRD1 and NMDAR1 in primary neurons(P＜0.05).(2)100 μmol·L-1 MⅤ treatment significantly inhibited the down-regulation of DRD1 and NMDAR1 expression induced by α-Syn PFF in primary neurons(P＜0.05).(3)The expression of DRD1 and NMDAR1 were both decreased by α-Syn PFF,while overexpression of NMDAR1 reversed the down-regulation of DRD1 level induced by α-Syn PFF.In conclusion,MⅤ alleviates α-Syn PFF induced down-regulation of DRD1 level by up-regulating NMDAR1 expression.This study provides a new experimental basis for elucidating the neuroprotective effect of MⅤ on PD,provides a theoretical foundation for the development of S.grosvenorii and its active component MⅤ as neuroprotective drugs,and provides a new scientific path for the in-depth development and value enhancement of Guangxi characteristic plants.