Lu Haofan, Li Yuntao, Zhang Yonggang, Qin Wen, Su Zhongzhou, Qiu Sheng, Zheng Lifang
Department of Neurosurgery, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University (Huzhou Central Hospital), 313000 Huzhou, Zhejiang, China.
Department of Neurosurgery, Huzhou Key Laboratory of Basic Research and Clinical Translation for Neuromodulation, 313000 Huzhou, Zhejiang, China.
Front Biosci (Landmark Ed). 2025 Apr 22;30(4):37810. doi: 10.31083/FBL37810.
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.
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.
VSIG4 ameliorated neurological deficits in ICH mice ( < 0.01), alleviated cerebral edema ( < 0.05), and increased glutathione ( < 0.05) and decreased superoxide dismutase (SOD) levels ( < 0.01) in the perihematomal area and LPS-stimulated RAW264.7 cells. It also reduced Malondialdehyde (MDA) accumulation ( < 0.01), alleviated oxidative stress, and decreased interleukin-1β (IL-1β) ( < 0.01) and tumor necrosis factor-alpha (TNF-α) levels ( < 0.01), thereby attenuating the inflammatory response. Additionally, treatment of LPS-stimulated RAW264.7 cells with VSIG4 resulted in less damage to HT22 cells ( < 0.05). To further validate the involvement of the NRF2/HO-1 pathway in VSIG4-mediated neuroprotection, brusatol (an NRF2 inhibitor) was administered.
Our study demonstrates the neuroprotective effect and mechanism of action of VSIG4 in ICH.
氧化应激和神经炎症是颅内出血（ICH）重要的继发性损伤机制。含V结构域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相关神经病理学中的可能作用。
在本研究中，检测了ICH小鼠模型和脂多糖（LPS）刺激的RAW264.7细胞中的VSIG4水平。此外，我们检测了氧化应激水平、促炎细胞因子产生、神经元损伤、炎症细胞活化、脑含水量和神经功能。我们在不同VSIG4水平的ICH小鼠和巨噬细胞中进行了这些检测。此外，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。
VSIG4改善了ICH小鼠的神经功能缺损（<0.01），减轻了脑水肿（<0.05），并增加了血肿周围区域和LPS刺激的RAW264.7细胞中谷胱甘肽水平（<0.05），降低了超氧化物歧化酶（SOD）水平（<0.01）。它还减少了丙二醛（MDA）积累（<0.01），减轻了氧化应激，并降低了白细胞介素-1β（IL-1β）水平（<0.01）和肿瘤坏死因子-α（TNF-α）水平（<0.01），从而减轻了炎症反应。此外，用VSIG4处理LPS刺激的RAW264.7细胞对HT22细胞的损伤较小（<0.05）。为了进一步验证NRF2/HO-1通路参与VSIG4介导的神经保护作用，给予了布罗索尤单抗（一种NRF2抑制剂）。
我们的研究证明了VSIG4在ICH中的神经保护作用及其作用机制。
