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马钱苷对MPTP诱导的帕金森病小鼠的神经保护作用:神经化学、胶质反应及自噬研究

Neuroprotective Effects of Loganin on MPTP-Induced Parkinson's Disease Mice: Neurochemistry, Glial Reaction and Autophagy Studies.

作者信息

Xu Yi-Da, Cui Chun, Sun Meng-Fei, Zhu Ying-Li, Chu Min, Shi Yun-Wei, Lin Stanley Li, Yang Xu-Sheng, Shen Yan-Qin

机构信息

Wuxi Medical School, Jiangnan University, Wuxi 214122, China.

Medical School of Nantong University, Nantong 226019, China.

出版信息

J Cell Biochem. 2017 Oct;118(10):3495-3510. doi: 10.1002/jcb.26010. Epub 2017 May 16.

DOI:10.1002/jcb.26010
PMID:28338241
Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease, involving resting tremor and bradykinesia, for which no recognized therapies or drugs are available to halt or slow progression. In recent years, natural botanic products have been considered relatively safe, with limited side effects, and are expected to become an important source for clinical mediation of PD in the future. Our study focuses on the ability of loganin, a compound derived from fruits of cornus, to mediate neuroprotection in a mouse model of PD. Mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) with a dosage of 30 mg/kg daily for 5 days to establish a subacute PD model and treated with loganin. Locomotor activity was assessed by a pole test, then mice were euthanized at 1 and 3 days after the last treatment, and brain tissue was prepared for subsequent assays. Loganin rescued decrease of dopamine levels and tyrosine hydroxylase (TH) expression in the striatum, and shortened total locomotor activity (TLA) time of mice. Furthermore, loganin alleviated microglia and astrocyte activation, and suppressed TNF-α and caspase-3 expression through a c-Abl-p38-NFκB pathway. Loganin also downregulated LC3-II and Drp1 expression, and decreased the level of acidic vesicular organelles (AVOs). Loganin exerts neuroprotective effects on MPTP-induced PD mice by decreasing inflammation, autophagy, and apoptosis, suggesting that loganin could serve as a therapeutic drug to ameliorate PD. J. Cell. Biochem. 118: 3495-3510, 2017. © 2017 Wiley Periodicals, Inc.

摘要

帕金森病(PD)是一种进行性神经退行性疾病,会出现静止性震颤和运动迟缓,目前尚无公认的疗法或药物可阻止或减缓其进展。近年来,天然植物产品被认为相对安全,副作用有限,有望在未来成为PD临床治疗的重要来源。我们的研究聚焦于山茱萸果实中提取的化合物马钱苷对PD小鼠模型的神经保护作用。给小鼠每日腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP),剂量为30 mg/kg,连续注射5天以建立亚急性PD模型,并给予马钱苷进行治疗。通过棒测试评估运动活性,然后在最后一次治疗后的第1天和第3天对小鼠实施安乐死,并制备脑组织用于后续检测。马钱苷挽救了纹状体中多巴胺水平和酪氨酸羟化酶(TH)表达的降低,并缩短了小鼠的总运动活性(TLA)时间。此外,马钱苷减轻了小胶质细胞和星形胶质细胞的激活,并通过c-Abl-p38-NFκB途径抑制了TNF-α和caspase-3的表达。马钱苷还下调了LC3-II和Drp1的表达,并降低了酸性囊泡细胞器(AVO)的水平。马钱苷通过减轻炎症、自噬和凋亡对MPTP诱导的PD小鼠发挥神经保护作用,表明马钱苷可作为改善PD的治疗药物。《细胞生物化学杂志》118: 3495 - 3510, 2017。© 2017威利期刊公司

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