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2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷对MPTP诱导的帕金森病小鼠保护作用的机制

Mechanism of the protective effect of 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside on MPTP-induced Parkinson's disease mice.

作者信息

Wu Gang, Dong Xiaolin, Li Qingyun, Li Yanping, Jin Furong, Lu Jingting, Han Chengda, Lin Lianbing

机构信息

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China.

Department of Neurology, Yan'an Hospital of Kunming City, Kunming, Yunnan, China.

出版信息

Histol Histopathol. 2025 Jul 16:18968. doi: 10.14670/HH-18-968.

Abstract

BACKGROUND AND PURPOSE

Parkinson's disease (PD) is a common neurodegenerative disorder with a complex pathogenesis. 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (TSG) is one of the main active components of Thunb., which has therapeutic effects in various neurodegenerative diseases. The aim of this study was to explore the influence of TSG on the PD process.

METHODS

The PD mouse model was constructed via the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD process was evaluated via behavioral tests, HE staining, immunohistochemistry, and immunofluorescence. The levels of related proteins and inflammatory factors were detected via western blotting and ELISA. The effect of TSG on the intestinal flora of MPTP-induced PD mice was evaluated through 16S rDNA sequencing.

RESULTS

TSG intervention can significantly alleviate motor dysfunction in PD mice, increase the number of TH-positive neurons in the substantia nigra, inhibit the accumulation of α-syn and glial cell activation, reduce the expression of the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, iNOS, and COX2 proteins in the substantia nigra and colon, inhibit neuroinflammation and intestinal inflammation, decrease the levels of LPS, LBP, TNF-α, IL-1β, and IL-6 in the serum, suppress systemic inflammation, reduce damage to the blood-brain barrier (BBB) and intestinal barrier in PD mice, and restore species diversity and abundance of the intestinal flora in PD mice to a certain extent.

CONCLUSION

TSG can improve motor coordination ability, systemic and neuroinflammatory levels, BBB injury, intestinal barrier injury, and the intestinal flora composition of PD mice, suggesting that TSG has a protective effect on MPTP-induced PD mice.

摘要

背景与目的

帕金森病(PD)是一种常见的神经退行性疾病,发病机制复杂。2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷(TSG)是何首乌的主要活性成分之一,对多种神经退行性疾病具有治疗作用。本研究旨在探讨TSG对PD进程的影响。

方法

通过使用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)构建PD小鼠模型。通过行为测试、HE染色、免疫组织化学和免疫荧光评估PD进程。通过蛋白质印迹法和酶联免疫吸附测定法检测相关蛋白和炎症因子水平。通过16S rDNA测序评估TSG对MPTP诱导的PD小鼠肠道菌群的影响。

结果

TSG干预可显著减轻PD小鼠的运动功能障碍,增加黑质中TH阳性神经元数量,抑制α-突触核蛋白的积累和胶质细胞活化,降低黑质和结肠中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6、诱导型一氧化氮合酶(iNOS)和环氧化酶2(COX2)蛋白的表达,抑制神经炎症和肠道炎症,降低血清中脂多糖(LPS)、脂多糖结合蛋白(LBP)、TNF-α、IL-1β和IL-6的水平,抑制全身炎症,减轻PD小鼠血脑屏障(BBB)和肠道屏障的损伤,并在一定程度上恢复PD小鼠肠道菌群的物种多样性和丰度。

结论

TSG可改善PD小鼠的运动协调能力、全身和神经炎症水平、BBB损伤、肠道屏障损伤及肠道菌群组成,提示TSG对MPTP诱导的PD小鼠具有保护作用。

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