浙江医学2025,Vol.47Issue(12):1233-1239,后插1,8.DOI:10.12056/j.issn.1006-2785.2025.47.12.2024-1301
姜黄素改善帕金森病小鼠行为缺陷的作用机制研究
Mechanism of curcumin in improving behavioral deficits in mice with Parkinson's disease
摘要
Abstract
Objective To explore the mechanism by which curcumin improves behavioral deficits in a mouse model of Parkinson's disease(PD).Methods A PD mouse model was established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).The motor abilities of the mice were assessed using the rotarod,pole,and open-field tests.The number of tyrosine hydroxylase(TH)-positive neurons in the substantia nigra was observed using immunofluorescence staining.The mRNA expression levels of inflammatory factors such as tumor necrosis factor α(TNF-α),interleukin-1 β(IL-1 β),and interleukin-6(IL-6)in the midbrain were detected using quantitative real-time reverse transcription polymerase chain reaction.The protein expression levels of genes related to the nuclear factor-κB(NF-κB)and nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathways were measured using Western blotting.Results The PD mouse model was successfully established,with significant motor impairments,including shortened rotarod retention time,prolonged pole test time,and decreased total distance traveled and time spent in the center of the open field.The number of TH-positive neurons in the substantia nigra of the model mice was reduced(P<0.05).Compared with the control group,the midbrain of the model mice exhibited neuroinflammation,characterized by increased mRNA expression levels of pro-inflammatory factors TNF-α,IL-1 β,IL-6,and NF-κB(all P<0.05),as well as elevated protein expression levels of NF-κB,p-NF-κB,NLRP3,and Caspase-1(all P<0.05).Compared with non-treated model mice,curcumin treatment at 80 mg/kg significantly improved behavioral deficits in the model mice,with increased rotarod retention time(P<0.05),decreased pole test time,and increased total distance traveled and time spent in the center of the open field(P<0.05).Immunofluorescence revealed a significant increase in the number of TH-positive dopaminergic neurons in the substantia nigra(P<0.05).The mRNA expression levels of TNF-α,IL-1 β,and NF-κB in the midbrain were significantly reduced(all P<0.05),and the protein expression levels of NF-κB,NLRP3 and Caspase-1 were decreased(all P<0.05).In contrast,curcumin treatment at 40 mg/kg did not show significant differences in any of the measured parameters compared with the untreated model mice(all P>0.05).Conclusion Curcumin can improve behavioral deficits in the PD mouse model and reverse the damage to TH-positive neurons in the substantia nigra.The therapeutic effect of 80 mg/kg curcumin is superior to that of 40 mg/kg,and this effect may be achieved by reducing the expression of neuroinflammatory factors in the brain.关键词
帕金森病小鼠/姜黄素/运动缺陷/神经炎症Key words
Mice with Parkinson's disease/Curcumin/Motor deficits/Neuroinflammation引用本文复制引用
李文惠,赵志弘,王莉娟,何金晶,刘玉婷,韩秋琴..姜黄素改善帕金森病小鼠行为缺陷的作用机制研究[J].浙江医学,2025,47(12):1233-1239,后插1,8.基金项目
上海市"科技创新行动计划"启明星培育(扬帆专项)(23YF1418200) (扬帆专项)
上海市卫生健康委员会卫生行业临床研究专项(青年项目)(20234Y0294) (青年项目)