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紫檀芪通过抑制 NLRP3 炎性小体和 Nox2 相关氧化应激减轻蛛网膜下腔出血后的早期脑损伤。

Pterostilbene Attenuates Early Brain Injury Following Subarachnoid Hemorrhage via Inhibition of the NLRP3 Inflammasome and Nox2-Related Oxidative Stress.

机构信息

Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an No. 1 Xinsi Road, Xi'an, 710038, China.

Department of Neurosurgery, General Hospital of Lanzhou Military Area Command, Lanzhou, 730050, China.

出版信息

Mol Neurobiol. 2017 Oct;54(8):5928-5940. doi: 10.1007/s12035-016-0108-8. Epub 2016 Sep 24.

DOI:10.1007/s12035-016-0108-8
PMID:27665283
Abstract

Pterostilbene (PTE), one of the polyphenols present in plants such as blueberries and grapes, has been suggested to have various effects, such as anti-oxidation, anti-apoptosis, and anti-cancer effects. Subarachnoid hemorrhage (SAH) is a severe neurological event known for its high morbidity and mortality. Recently, early brain injury (EBI) has been reported to play a significant role in the prognosis of patients with SAH. The present study aimed to investigate whether PTE could attenuate EBI after SAH was induced in C57BL/6 J mice. We also studied possible underlying mechanisms. After PTE treatment, the neurological score and brain water content of the mice were assessed. Oxidative stress and neuronal injury were also evaluated. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity was assessed using western blot analysis. Our results indicated that PTE treatment reduces the SAH grade, neurological score, and brain water content following SAH. PTE treatment also reduced NLRP3 inflammasome activation. PTE alleviated the oxidative stress following SAH as evidenced by the dihydroethidium staining, superoxide dismutase activity, malondialdehyde content, 3-nitrotyrosie and 8-hydroxy-2-deoxyguanosine levels, and gp91 and 4-hydroxynonenal expression levels. Additionally, PTE treatment reduced neuronal apoptosis. In conclusion, our study suggests that PTE attenuates EBI following SAH possibly via the inhibition of NLRP3 inflammasome and Nox2-related oxidative stress.

摘要

紫檀芪(PTE)是存在于蓝莓和葡萄等植物中的一种多酚,被认为具有多种作用,如抗氧化、抗细胞凋亡和抗癌作用。蛛网膜下腔出血(SAH)是一种严重的神经系统事件,以高发病率和死亡率为特征。最近,早期脑损伤(EBI)被报道在 SAH 患者的预后中起重要作用。本研究旨在探讨 PTE 是否能减轻 C57BL/6J 小鼠诱导的 SAH 后的 EBI,并研究可能的潜在机制。在 PTE 治疗后,评估了小鼠的神经评分和脑含水量。氧化应激和神经元损伤也进行了评估。使用 Western blot 分析评估核苷酸结合寡聚化结构域样受体家族吡喃结构域包含蛋白 3(NLRP3)炎性小体的活性。我们的结果表明,PTE 治疗可降低 SAH 后 SAH 等级、神经评分和脑含水量。PTE 治疗还降低了 NLRP3 炎性小体的激活。PTE 减轻了 SAH 后的氧化应激,这表现在二氢乙啶染色、超氧化物歧化酶活性、丙二醛含量、3-硝基酪氨酸和 8-羟基-2-脱氧鸟苷水平以及 gp91 和 4-羟基壬烯醛表达水平的降低。此外,PTE 治疗减少了神经元凋亡。总之,我们的研究表明,PTE 通过抑制 NLRP3 炎性小体和 Nox2 相关氧化应激来减轻 SAH 后的 EBI。

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