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白藜芦醇对蛛网膜下腔出血后嗅球损伤的神经保护作用。

Neuroprotective Effects of Piceatannol on Olfactory Bulb Injury after Subarachnoid Hemorrhage.

机构信息

Faculty of Medicine, Department of Neurosurgery, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.

Faculty of Medicine, Department of Biophysics, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.

出版信息

Mol Neurobiol. 2023 Jul;60(7):3695-3706. doi: 10.1007/s12035-023-03306-x. Epub 2023 Mar 18.

Abstract

Subarachnoid hemorrhage (SAH) accounts for 5% of all stroke cases and is responsible for significant permanent brain and neurological damage within the first few days. Loss of smell is one of those neurological disorders following olfactory bulb injury after SAH. Olfaction plays a critical role in several aspects of life. The primary underlying mechanism of olfactory bulb (OB) injury and loss of smell after SAH remains unknown. Piceatannol (PIC), a natural stilbene, possesses anti-inflammatory and anti-apoptotic effects against various diseases. In this study, we aimed to investigate the potential therapeutic effects of PIC on OB injury following SAH at molecular mechanism based on SIRT1, inflammatory (TNF-α, IL1-β, NF-κB, IL-6, TLR4), and apoptosis (p53, Bax, Bcl-2, caspase-3)-related gene expression markers and histopathology level; 27 male Wistar Albino rats were used in a pre-chiasmatic subarachnoid hemorrhage model. Animals were divided into groups (n = 9): SHAM, SAH, and PIC. Garcia's neurological examination, brain water content, RT-PCR, histopathology, and TUNEL analyses were performed in all experimental groups with OB samples. Our results indicated that PIC administration significantly suppressed inflammatory molecules (TNF-α, IL-6, IL1-β, TLR4, NF-κB, SIRT1) and apoptotic molecules (caspase-3, p53, Bax). We also evaluated edema levels and cell damage in OB injury after SAH. Ameliorative effects of PIC are also observed at the histopathology level. Garcia's neurological score test performed a neurological assessment. This study is the first to demonstrate the neuroprotective effects of PIC on OB injury after SAH. It suggests that PIC would be a potential therapeutic agent for alleviating OB injury after SAH.

摘要

蛛网膜下腔出血(SAH)占所有中风病例的 5%,并在最初几天内导致大脑和神经系统的严重永久性损伤。嗅觉丧失是 SAH 后嗅球损伤的神经系统疾病之一。嗅觉在生活的几个方面起着关键作用。SAH 后嗅球(OB)损伤和嗅觉丧失的基本潜在机制尚不清楚。白皮杉醇(PIC)是一种天然芪类化合物,具有抗炎和抗凋亡作用,可用于治疗多种疾病。在这项研究中,我们旨在基于 SIRT1、炎症(TNF-α、IL1-β、NF-κB、IL-6、TLR4)和凋亡(p53、Bax、Bcl-2、caspase-3)相关基因表达标志物和组织病理学水平,研究 PIC 对 SAH 后 OB 损伤的潜在治疗作用;使用了 27 只雄性 Wistar 白化大鼠进行视交叉前蛛网膜下腔出血模型。动物分为 3 组(n=9):SHAM、SAH 和 PIC。对所有实验组的 OB 样本进行了 Garcia 神经学检查、脑水含量、RT-PCR、组织病理学和 TUNEL 分析。我们的结果表明,PIC 给药可显著抑制炎症分子(TNF-α、IL-6、IL1-β、TLR4、NF-κB、SIRT1)和凋亡分子(caspase-3、p53、Bax)。我们还评估了 SAH 后 OB 损伤的水肿水平和细胞损伤。PIC 在组织病理学水平也表现出改善作用。Garcia 神经学评分测试进行了神经学评估。这项研究首次证明了 PIC 对 SAH 后 OB 损伤的神经保护作用。这表明 PIC 可能是缓解 SAH 后 OB 损伤的潜在治疗药物。

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