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研究密褶红菇多糖通过降低 NLRP3 炎性小体的表达缓解 PD 小鼠神经行为学的作用。

Study on antrodia camphorata polysaccharide in alleviating the neuroethology of PD mice by decreasing the expression of NLRP3 inflammasome.

机构信息

Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, JiaXing, China.

Department of Central Laboratory, The Second Affiliated Hospital of Jiaxing University, JiaXing, China.

出版信息

Phytother Res. 2019 Sep;33(9):2288-2297. doi: 10.1002/ptr.6388. Epub 2019 Jul 29.

DOI:10.1002/ptr.6388
PMID:31359520
Abstract

Parkinson's disease (PD) is a neurodegenerative disease, and the role of neuroinflammation in the pathogenesis and progression of PD has been confirmed. The polysaccharides and triterpenoids of antrodia camphorata (a polyporous fungus) harbor diverse and powerful pharmacological effects. In this study, 6-hydroxydopamine was used to construct a PD mouse model. After antrodia camphorata polysaccharide (ACP) intervention, neurobehavioral changes were detected, neurotransmitter changes in striatum were determined by high-performance liquid chromatography, the alterations of striatal NOD-like receptor pyrin domain containing three (NLRP3) were examined by immunohistochemistry, and the expression of NLRP3, IL-1β, Caspase-1, and proCaspase-1 were detected by western blot. To be specific, the items of neurobehavioral test included open field activity, rotary test, pole test, gait analysis, and swimming test. As a result, 6-hydroxydopamine could lead to PD-like lesions, including tremor, stiffness, attenuated spontaneous activity, and bradykinesia in mice, and the expression of tyrosine hydroxylase in the striatum was decreased. After ACP intervention, the neuroethology of mice was significantly improved, as demonstrated by the elevated levels of dopamine in the striatum and the decreased expression of dopamine in the striatum in NLRP3 inflammasome. NLRP3 inflammasome played an important role in neuroinflammation in PD mice. ACP could reduce the activation of NLRP3 and expression of related inflammatory factors.

摘要

帕金森病(PD)是一种神经退行性疾病,神经炎症在 PD 的发病机制和进展中的作用已得到证实。樟芝(多孔菌科真菌)的多糖和三萜类化合物具有多样而强大的药理作用。本研究采用 6-羟多巴胺构建 PD 小鼠模型,经樟芝多糖(ACP)干预后,检测神经行为学变化,高效液相色谱法测定纹状体神经递质变化,免疫组化法检测纹状体 NOD 样受体含pyrin 结构域蛋白 3(NLRP3)的变化,Western blot 检测 NLRP3、IL-1β、Caspase-1、proCaspase-1 的表达。具体来说,神经行为学测试项目包括旷场活动、转棒试验、棒状试验、步态分析和游泳试验。结果表明,6-羟多巴胺可导致小鼠出现 PD 样病变,包括震颤、僵硬、自发活动减弱和运动迟缓,纹状体酪氨酸羟化酶表达降低。ACP 干预后,小鼠的神经行为学明显改善,表现为纹状体多巴胺水平升高,NLRP3 炎性小体中多巴胺表达降低。NLRP3 炎性小体在 PD 小鼠的神经炎症中发挥重要作用,ACP 可降低 NLRP3 的激活和相关炎症因子的表达。

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