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瑞因通过 MAPK/IκB 信号通路抑制 BV2 小胶质细胞 M1 极化,减轻神经炎症引起的神经毒性。

Rhein inhibits M1 polarization of BV2 microglia through MAPK/IκB signalling pathway and reduces neurotoxicity caused by neuroinflammation.

机构信息

The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Yichang Central People's Hospital, Yichang, China.

出版信息

Int J Dev Neurosci. 2024 Oct;84(6):533-545. doi: 10.1002/jdn.10352. Epub 2024 Jun 10.

DOI:10.1002/jdn.10352
PMID:38858813
Abstract

BACKGROUND

Rhein is an anthraquinone compound with anti-inflammatory pharmacological activity. It has been found to play a neuroprotective role in neurological diseases, but the neuroprotective mechanism of rhein remains unclear.

METHODS

SH-SY5Y cells serving as neuron-like cells and BV2 microglia were used. The toxicity of rhein on BV2 microglia and the viability of SH-SY5Y cells were measured by CCK-8 assay. The mRNA expression and secretion of pro-inflammatory cytokines were detected by qPCR and ELISA. Iba1, CD86 and pathway signalling protein in BV2 microglia were assessed by Western blot and immunofluorescence. Apoptosis of SH-SY5Y cells exposed to neuroinflammation was analysed through flow cytometry.

RESULTS

Rhein inhibited MAPK/IκB signalling pathways. Further studies revealed that rhein inhibited the production of pro-inflammatory cytokines TNF-α, IL-6, IL-1β and iNOS in BV2 cells and also inhibited the expression of M1 polarization markers Iba1 and CD86 in BV2 cells. Furthermore, rhein reduced the apoptotic rate and restored cell viability of SH-SY5Y cells exposed to neuroinflammation.

CONCLUSIONS

Our study demonstrated that rhein inhibited microglia M1 polarization via MAPK/IκB signalling pathway and protected nerve cells through suppressing neuroinflammation.

摘要

背景

大黄酸是一种具有抗炎药理活性的蒽醌类化合物。它已被发现在神经退行性疾病中发挥神经保护作用,但大黄酸的神经保护机制尚不清楚。

方法

本研究采用神经元样细胞 SH-SY5Y 和小胶质细胞 BV2 作为研究对象。通过 CCK-8 法测定大黄酸对 BV2 小胶质细胞的毒性作用和 SH-SY5Y 细胞的活力。通过 qPCR 和 ELISA 检测促炎细胞因子的 mRNA 表达和分泌。通过 Western blot 和免疫荧光法评估 BV2 小胶质细胞中 Iba1、CD86 和通路信号蛋白的表达。通过流式细胞术分析神经炎症暴露的 SH-SY5Y 细胞的凋亡情况。

结果

大黄酸抑制 MAPK/IκB 信号通路。进一步研究表明,大黄酸抑制了 BV2 细胞中促炎细胞因子 TNF-α、IL-6、IL-1β和 iNOS 的产生,同时抑制了 BV2 细胞中 M1 极化标志物 Iba1 和 CD86 的表达。此外,大黄酸降低了神经炎症暴露的 SH-SY5Y 细胞的凋亡率并恢复了细胞活力。

结论

本研究表明,大黄酸通过 MAPK/IκB 信号通路抑制小胶质细胞 M1 极化,并通过抑制神经炎症来保护神经细胞。

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