龙胆苦苷通过NF-κB/NLRP3/GSDMD通路介导小胶质细胞焦亡,减轻帕金森病的神经炎症。

IF 2 4区 生物学 Q3 CELL BIOLOGY
Histology and histopathology Pub Date : 2025-09-01 Epub Date: 2025-01-27 DOI:10.14670/HH-18-879
Hong Shen, Hui Song, Qiang Sun
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引用次数: 0

摘要

目的:通过体外和体内实验,评价龙胆苦苷(GPS)对帕金森病(PD)的治疗潜力,重点阐明其作用机制。方法:为此,采用1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)建立C57BL6小鼠PD模型,随后评估行为改变、病理改变、小胶质细胞激活和神经炎症。同时,通过将BV-2小鼠小胶质细胞暴露于1-甲基-4-苯基吡啶(MPP+),建立细胞PD模型。采用酶联免疫吸附法(ELISA)测定促炎分子的表达,采用caspase-1/PI双染色流式细胞术分析焦亡现象。免疫印迹法检测核因子κB (NF-κB)/ nod样受体热蛋白结构域相关蛋白3 (NLRP3)/气皮蛋白D (GSDMD)信号通路关键因子的表达。结果:研究结果显示,GPS可有效减轻mptp诱导的PD小鼠模型的运动障碍、神经损伤、小胶质细胞激活和神经炎症。此外,GPS还能保护BV-2细胞免受MPP+诱导的炎症细胞因子的产生和焦亡。机制研究表明,在体内和体外,GPS可能通过灭活NF-κB/NLRP3/ gsdmd介导的焦亡通路来发挥其神经保护作用。结论:GPS通过抑制小胶质细胞介导的神经炎症和焦凋亡,对帕金森病具有神经保护作用,提示其可能成为帕金森病治疗的良好药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gentiopicroside alleviates neuroinflammation in Parkinson's disease by mediating microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway.

Objective: The study aimed to evaluate the therapeutic potential of gentiopicroside (GPS) in Parkinson's disease (PD) through both in vitro and in vivo experiments, focusing on elucidating the underlying mechanisms of its action.

Methods: To achieve this, a PD model was established in C57BL6 mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), followed by assessment of behavioral changes, pathological alterations, microglial activation, and neuroinflammation. Simultaneously, a cellular PD model was developed in the BV-2 mouse microglia cell line by exposing them to 1-methyl-4-phenyl-pyridinium (MPP+). The expression of pro-inflammatory molecules was quantified using enzyme-linked immunosorbent assay (ELISA), while pyroptosis was analyzed by flow cytometry with caspase-1/PI double staining. The expression of key factors in the nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway was determined by immunoblotting.

Results: The findings revealed that GPS effectively mitigated motor deficits, neurological impairments, microglial activation, and neuroinflammation in the MPTP-induced mouse model of PD. Additionally, GPS protected BV-2 cells from MPP+-induced inflammatory cytokine production and pyroptosis. Mechanistic studies indicated that GPS may exert its neuroprotective effects by inactivating the NF-κB/NLRP3/GSDMD-mediated pyroptotic pathway in both in vivo and in vitro settings.

Conclusion: GPS exhibits neuroprotective effects in PD by suppressing microglia-mediated neuroinflammation and pyroptosis, suggesting its potential as a favorable therapeutic agent for PD treatment.

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来源期刊
Histology and histopathology
Histology and histopathology 生物-病理学
CiteScore
3.90
自引率
0.00%
发文量
232
审稿时长
2 months
期刊介绍: HISTOLOGY AND HISTOPATHOLOGY is a peer-reviewed international journal, the purpose of which is to publish original and review articles in all fields of the microscopical morphology, cell biology and tissue engineering; high quality is the overall consideration. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year (more than 1,300 pages, approximately 90 original works and 40 reviews). Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online.
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