Neuroprotective Effects of Paeoniflorin on 6-OHDA-Lesioned Rat Model of Parkinson's Disease
Neuroprotective Effects of Paeoniflorin on 6-OHDA-Lesioned Rat Model of Parkinson's Disease
复制标题
芍药甙对6-OHDA损伤帕金森病大鼠模型的神经保护作用
DOI：
10.1007/s11064-016-2011-0
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发表时间：
2016-11-01
影响因子：
4.4
通讯作者：
Liu, Chun-Feng
中科院分区：
文献类型：
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作者：
Gu, Xiao-Su;Wang, Fen;Liu, Chun-Feng
芍药苷(PF)是从牡丹根中提取的主要活性成分，是治疗神经退行性疾病，尤其是帕金森病(PD)的传统中药。帕金森病患者多巴胺能神经元的变性可能与酸敏感离子通道的病理性激活有关。因此，我们设计了一系列实验来评估PF的治疗作用，并测试其作用是否与其对ASIC1a的抑制作用有关。我们发现，在6-羟基多巴胺(6-OHDA)诱导的帕金森病大鼠模型中，全身性给予PF或ASICs阻滞剂(Psalmooxin-1和阿米洛利)可以改善帕金森病大鼠的行为症状，延缓DA神经元的丢失，并减轻多巴胺(DA)及其代谢产物的减少。此外，我们的数据显示，与ASICs阻滞剂一样，PF可以调节ASIC1a的表达，降低α-突触核蛋白(α-SYN)的水平，并改善自噬功能障碍。进一步的实验表明，ASIC1a基因敲除下调了6-OHDA处理的ASIC1a沉默的PC12细胞的α-SYN水平，并减轻了自噬损伤。综上所述，这些发现表明，PF促进了α-SYN的自噬降解，从而保护DA神经元免受6-OHDA的神经毒性。这些发现也提供了实验证据，表明PF可能通过作用于ASIC1a而对帕金森病具有神经保护作用，并且ASIC1a可能参与了帕金森病的发病。
Paeoniflorin (PF) is the main active component extracted from the roots of Paeonialactiflora, a traditional Chinese medicine used for the treatment of neurodegenerative disorders, especially Parkinson's disease (PD). The degeneration of dopaminergic (DA-) neurons in PD may be caused by pathological activation of acid-sensing ion channels (ASICs). Thus, we designed a series of experiments to evaluate the therapeutic effects of PF and to test whether its effects are related to its inhibitory effect on ASIC1a. We found that systemic administration of PF or ASICs blockers (psalmotoxin-1 and amiloride) improved behavioral symptoms, delayed DA-neuronal loss and attenuated the reduction of dopamine (DA) and its metabolites in a rat model of 6-hydroxydopamine (6-OHDA)-induced PD. In addition, our data showed that PF, like ASICs blockers, regulated the expression of ASIC1a, decreased the level of alpha-synuclein (alpha-SYN), and improved autophagic dysfunction. Further experiments showed that ASIC1a knockdown down-regulated the alpha-SYN level and alleviated the autophagic injury in the 6-OHDA-treated ASIC1a-silenced PC12 cells. In summary, these findings indicate that PF enhanced the autophagic degradation of alpha-SYN and, thus, protected DA-neurons against the neurotoxicity caused by 6-OHDA. These findings also provide experimental evidence that PF may be a neuroprotectant for PD by acting on ASIC1a and that ASIC1a may be involved in the pathogenesis of PD.