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虫草素通过抑制 TLR/NF-κB 信号通路减轻 MPTP 诱导的帕金森病。

Cordycepin mitigates MPTP-induced Parkinson's disease through inhibiting TLR/NF-κB signaling pathway.

机构信息

Department of Ward Service Management, Heze Municiple Hospital, Heze, Shandong, China.

Department of Neurology, Heze Municiple Hospital, Heze, Shandong, China.

出版信息

Life Sci. 2019 Apr 15;223:120-127. doi: 10.1016/j.lfs.2019.02.037. Epub 2019 Feb 18.

DOI:10.1016/j.lfs.2019.02.037
PMID:30790609
Abstract

Parkinson's disease (PD) is a neurodegenerative disease with movement disorder. PD is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra. Cordycepin, a small molecule extracted from cordyceps sinensis, has neuroprotective, anti-inflammatory, antioxidant and anti-tumor properties. In this study, we explored its possible beneficial effects on PD. PD rat models and cell models were established via 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP) injection and LPS treatment respectively, and cordycepin was administered. The motor functions of rats were examined, and the tyrosine hydroxylase (TH)-positive DA neurons and Iba1-positive microglia were detected by immunohistochemical and immunofluorescence staining. The expression levels of inflammatory and oxidative stress-related factors were also measured in vivo and in vitro. In addition, the TLR/NF-κB pathway was investigated to explore the mechanism. We found that in vivo, MPTP injection introduced motor disorders, the loss of DA neurons and the activation of TLR/NF-κB signaling pathway. Cordycepin treatment alleviated these MPTP-induced changes. In vitro, the results were confirmed in Lipopolysaccharide (LPS)-induced cells. Moreover, cordycepin mitigated the cytotoxic effects on PC12 cells produced by microglia. In conclusion, cordycepin alleviated PD symptoms by inhibiting TLR/NF-κB signaling pathway in vivo and in vitro.

摘要

帕金森病(PD)是一种以运动障碍为特征的神经退行性疾病。PD 的特征是黑质中多巴胺能(DA)神经元的丧失。虫草素是从蛹虫草中提取的一种小分子,具有神经保护、抗炎、抗氧化和抗肿瘤作用。在这项研究中,我们探讨了它对 PD 的可能有益影响。通过 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)注射和 LPS 处理分别建立 PD 大鼠模型和细胞模型,并给予虫草素。检查大鼠的运动功能,并通过免疫组织化学和免疫荧光染色检测酪氨酸羟化酶(TH)阳性 DA 神经元和 Iba1 阳性小胶质细胞。还在体内和体外测量了炎症和氧化应激相关因子的表达水平。此外,还研究了 TLR/NF-κB 通路,以探讨其机制。我们发现,体内注射 MPTP 会引起运动障碍、DA 神经元丧失和 TLR/NF-κB 信号通路的激活。虫草素治疗减轻了这些 MPTP 引起的变化。在 LPS 诱导的细胞中也证实了体外结果。此外,虫草素减轻了小胶质细胞对 PC12 细胞的细胞毒性作用。总之,虫草素通过抑制 TLR/NF-κB 信号通路在体内和体外缓解 PD 症状。

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