大黄酚通过调控NRF2/ARE/GSDMD信号通路抑制缺血/再灌注诱导的神经元焦亡

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2025-08-14 DOI:10.1016/j.tice.2025.103082

Feijian Zeng , Yao Liang , Yufei Wei , Yonghua Huang , Yan Yan , Yongjun Wu , Guihua Huang

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引用次数: 0

摘要

大黄酚（CHR）已被证明对缺血性脑卒中（IS）具有显著的神经保护作用。本研究旨在探讨CHR对脑缺血再灌注（I/R）的影响。方法采用smcao /R法建立小鼠IS模型。采用尼氏染色进行组织学分析。TUNEL染色检测神经元丢失。采用OGD/R法建立体外脑I/R损伤模型。采用RT-qPCR和Western blot检测基因表达。ELISA法检测细胞因子释放量。采用CCK-8法、LDH法、流式细胞术、TUNEL染色检测细胞功能。采用荧光素酶和ChIP法检测GSDMD转录。结果schr可减轻OGD/R诱导的大鼠神经元损伤，抑制氧化应激、炎症反应和神经元焦亡。CHR促进NRF2/ARE信号的激活。NRF2抑制GSDMD的转录，导致其下调。然而，NRF2信号的抑制导致神经元损伤和焦亡。结论schr通过调控NRF2/ARE/GSDMD信号通路，对脑I/R损伤所致的神经元损失具有保护作用。因此，CHR可能是治疗脑I/R损伤的一种有前景的策略。

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Chrysophanol inhibits ischemia/reperfusion-induced neuronal pyroptosis by regulating NRF2/ARE/GSDMD signaling pathway

Background

Chrysophanol (CHR) has been shown to afford significant neuroprotection on ischemic stroke (IS). This study aimed to investigate the effects of CHR on cerebral ischemia/reperfusion (I/R).

Methods

MCAO/R was used to establish mouse IS model. Histological analysis was performed using Nissl staining. Neuronal loss was detected using TUNEL staining. OGD/R was used to establish in vitro cerebral I/R injury model. Gene expression was detected using RT-qPCR and Western blot. Cytokine release was detected using ELISA. Cellular functions were detected using CCK-8 assay, LDH assay, flow cytometry, and TUNEL staining. GSDMD transcription was detected using luciferase and ChIP assays.

Results

CHR alleviated OGD/R induced neuronal damage, as well as inhibited oxidative stress, inflammatory response, and neuronal pyroptosis in vivo and in vitro. CHR promoted the activation of NRF2/ARE signaling. NRF2 inhibited the transcription of GSDMD, resulting in its downregulation. However, inhibition of NRF2 signaling contributed to neuronal damage and pyroptosis.

Conclusions

CHR protects against cerebral I/R injury-induced neuronal loss by regulating NRF2/ARE/GSDMD signaling pathway. Therefore, CHR may be a promising strategy for cerebral I/R injury.

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来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.