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四羟基二苯乙烯葡萄糖苷对 MPTP 帕金森病小鼠模型的神经保护作用。

Neuroprotection by tetrahydroxystilbene glucoside in the MPTP mouse model of Parkinson's disease.

机构信息

Department of Scientific Research, Hong Hui Hospital, Xi'an Jiaotong University College of Medicine, Xi'an 710054, China.

出版信息

Toxicol Lett. 2013 Oct 24;222(2):155-63. doi: 10.1016/j.toxlet.2013.07.020. Epub 2013 Aug 1.

Abstract

Our in vitro experiments suggested that tetrahydroxystilbene glucoside (TSG) affords a significant neuroprotective effect against MPP⁺-induced damage and apoptosis in PC12 cells though activation of the PI3K/Akt pathway. This study was aimed to investigate the potential neuroprotective effect of TSG in 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP)-treated mouse model of Parkinson's disease (PD). We found that treatment of TSG protected dopaminergic neurons by preventing MPTP-induced decreases in substantia nigra tyrosine hydroxylase (TH)-positive cells and striatal dopaminergic transporter (DAT) protein levels. Furthermore, it was also associated with increasing striatal Akt and GSK3β phosphorylation, up-regulation of the Bcl-2/BAD ratio, and inhibition of the activation of caspase-9 and caspase-3. These results showed that TSG promoted dopamine neuron survival in vivo, the PI3K/Akt signaling pathway may have mediated the protection of TSG against MPTP, suggesting that TSG treatment might represent a neuroprotective treatment for PD.

摘要

我们的体外实验表明,四羟基二苯乙烯葡萄糖苷(TSG)通过激活 PI3K/Akt 通路,对 MPP⁺诱导的 PC12 细胞损伤和凋亡提供显著的神经保护作用。本研究旨在探讨 TSG 在 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)小鼠模型中的潜在神经保护作用。我们发现,TSG 通过防止 MPTP 诱导的黑质酪氨酸羟化酶(TH)阳性细胞和纹状体多巴胺转运蛋白(DAT)蛋白水平下降,来保护多巴胺能神经元。此外,它还与增加纹状体 Akt 和 GSK3β磷酸化、上调 Bcl-2/BAD 比值以及抑制 caspase-9 和 caspase-3 的激活有关。这些结果表明,TSG 促进了体内多巴胺神经元的存活,PI3K/Akt 信号通路可能介导了 TSG 对 MPTP 的保护作用,提示 TSG 治疗可能代表 PD 的一种神经保护治疗方法。

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