首页|Rotigotine长链酯改善帕金森病小鼠嗅觉障碍的机制

Rotigotine长链酯改善帕金森病小鼠嗅觉障碍的机制

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本实验旨在探讨Rotigotine长链酯(RLCE)对帕金森病(PD)嗅觉障碍的改善作用机制.50只C57小鼠随机分为正常组,模型组,RLCE低(11.2 mg·kg-1)、中(22.4 mg· kg-1)、高(44.8 mg·kg-1)剂量组,采用1-甲基-4-苯基-1,2,3,6,-四氢吡啶(MPTP)诱导PD小鼠模型,予以RLCE进行治疗.通过埋丸实验和木块实验观察RLCE对PD小鼠嗅觉障碍的改善作用;免疫组化法(IHC)检测小鼠黑质和嗅球的酪氨酸羟化酶(TH)阳性细胞及嗅球α-突触核蛋白(α-syn)、磷酸化α-突触核蛋白(P-α-syn)的表达水平;Western Blot实验检测小鼠嗅球α-syn、P-α-syn及炎症相关因子钙离子接头蛋白(IBA1)、胶质纤维酸性蛋白(GFAP)、一氧化氮合酶(iNOS)的表达水平.结果表明,RLCE可以明显改善PD小鼠的嗅觉障碍,增加黑质TH神经元的表达,降低嗅球TH神经元的表达,降低嗅球α-syn、P-α-syn以及GFAP、iNOS、IBA1的表达.结果提示,RLCE对PD小鼠的嗅觉障碍具有明显的改善作用,该作用可能与其减轻神经炎症反应,抑制α-syn的聚集及磷酸化、降低嗅球TH神经元的代偿性增加有关.
Mechanism of Rotigotine Long Chain Ester for Improving Olfactory Dysfunction of Parkinsonian Mice
The aim of this experiment is to investigate the mechanism of Rotigotine long chain ester(RLCE)for im-proving olfactory dysfunction of Parkinson's disease(PD).Fifty C57 mice are randomly divided into normal group,model group,RLCE low(11.2 mg·kg-1),medium(22.4 mg·kg-1)and high(44.8 mg·kg-1)dose groups.MPTP-induced PD mouse model is used and RLCE is administered for treatment.The improvement of RLCE on ol-factory dysfunction in mice is observed by Buried Pellet Test and Wood Block Test.Immunohistochemistry(IHC)is used to detect tyrosine hydroxylase(TH)-positive cells in the substantia nigra and olfactory bulb,and the ex-pression levels of α-synuclein(α-syn)and phospho-synuclein(P-α-syn)in olfactory bulb.Western blot is used to detect the expression of α-syn,P-α-syn and inflammation-related factors calcium adaptor protein(IBA1),glial fi-brillary acidic protein(GFAP),and nitric oxide lyase(iNOS)in olfactory bulb.The results show that,RLCE can significantly improve olfactory dysfunction,increase the expression of TH neurons in substantia nigra,decrease the expression of TH neurons in olfactory bulb,and decrease the expression of α-syn,P-α-syn as well as GFAP,iN-OS,and IBA1 in olfactory bulb of mice.The results suggest that RLCE can significantly improve olfactory dysfunc-tion in PD mice,which may be related to the alleviation of neuroinflammatory response,the inhibition of the aggre-gation and phosphorylation of α-syn,and the decrease of the expression of TH neurons in the olfactory bulb.

Parkinson's diseaseolfactory impairmentinflammationRotigotine long chain ester

郭春敏、张红、田付港、于昕

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烟台大学药学院,分子药理和药物评价教育部重点实验室(烟台大学),新型制剂与生物技术药物研究山东省高校协同创新中心,山东烟台,264005

帕金森病 嗅觉障碍 炎症 Rotigotine长链酯

山东省"泰山学者"项目

2207070499

2024

烟台大学学报(自然科学与工程版)
烟台大学

烟台大学学报(自然科学与工程版)

影响因子:0.373
ISSN:1004-8820
年,卷(期):2024.37(1)
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