VSIG4 Alleviates Intracranial Hemorrhage Injury by Regulating Oxidative Stress and Neuroinflammation in Macrophages via the NRF2/HO-1 Signaling Pathway.

IF 3.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Haofan Lu, Yuntao Li, Yonggang Zhang, Wen Qin, Zhongzhou Su, Sheng Qiu, Lifang Zheng
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Abstract

Background: Oxidative stress and neuroinflammation are important secondary injury mechanisms in intracranial hemorrhage (ICH). V-set and immunoglobulin domain-containing 4 (VSIG4) has an inhibitory effect on oxidative stress and the inflammatory response. This study aimed to explore the possible role of VSIG4 in ICH-related neuropathology.

Methods: In this study, VSIG4 levels were investigated in an ICH mouse model and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Moreover, we examined oxidative stress levels, pro-inflammatory cytokine production, neuronal damage, inflammatory cell activation, brain water content, and neurological function. We performed these assays in ICH mice and macrophages with different VSIG4 levels. Additionally, the critical role of the nuclear factor erythroid 2 related factor 2/heme oxygenase-1 (NRF2/HO-1) signaling pathway in VSIG4 function was verified.

Results: VSIG4 ameliorated neurological deficits in ICH mice (p < 0.01), alleviated cerebral edema (p < 0.05), and increased glutathione (p < 0.05) and decreased superoxide dismutase (SOD) levels (p < 0.01) in the perihematomal area and LPS-stimulated RAW264.7 cells. It also reduced Malondialdehyde (MDA) accumulation (p < 0.01), alleviated oxidative stress, and decreased interleukin-1β (IL-1β) (p < 0.01) and tumor necrosis factor-alpha (TNF-α) levels (p < 0.01), thereby attenuating the inflammatory response. Additionally, treatment of LPS-stimulated RAW264.7 cells with VSIG4 resulted in less damage to HT22 cells (p < 0.05). To further validate the involvement of the NRF2/HO-1 pathway in VSIG4-mediated neuroprotection, brusatol (an NRF2 inhibitor) was administered.

Conclusion: Our study demonstrates the neuroprotective effect and mechanism of action of VSIG4 in ICH.

VSIG4通过NRF2/HO-1信号通路调节巨噬细胞氧化应激和神经炎症,减轻颅内出血损伤。
背景:氧化应激和神经炎症是颅内出血(ICH)的重要继发损伤机制。V-set和免疫球蛋白结构域- 4 (VSIG4)对氧化应激和炎症反应具有抑制作用。本研究旨在探讨VSIG4在ich相关神经病理中的可能作用。方法:采用脑缺血大鼠模型和脂多糖(LPS)刺激的RAW264.7细胞检测VSIG4水平。此外,我们还检测了氧化应激水平、促炎细胞因子产生、神经元损伤、炎症细胞激活、脑含水量和神经功能。我们在不同VSIG4水平的脑出血小鼠和巨噬细胞中进行了这些检测。此外,我们还验证了核因子红细胞2相关因子2/血红素加氧酶-1 (NRF2/HO-1)信号通路在VSIG4功能中的关键作用。结果:VSIG4改善脑出血小鼠神经功能缺损(p < 0.01),减轻脑水肿(p < 0.05),提高血周区谷胱甘肽(p < 0.05),降低lps刺激的RAW264.7细胞超氧化物歧化酶(SOD)水平(p < 0.01)。降低丙二醛(MDA)积累(p < 0.01),减轻氧化应激,降低白细胞介素-1β (IL-1β) (p < 0.01)和肿瘤坏死因子-α (TNF-α)水平(p < 0.01),减轻炎症反应。此外,用VSIG4处理lps刺激的RAW264.7细胞对HT22细胞的损伤较小(p < 0.05)。为了进一步验证NRF2/HO-1通路在vsig4介导的神经保护中的作用,研究人员给药brusatol(一种NRF2抑制剂)。结论:本研究证实了VSIG4对脑出血大鼠的神经保护作用及其机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
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