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神经黏附因子通过抑制神经元凋亡和 NLRP3 炎性小体在急性缺血性脑卒中大鼠模型中发挥神经保护作用。

Neuritin has a neuroprotective role in the rat model of acute ischemia stroke by inhibiting neuronal apoptosis and NLRP3 inflammasome.

机构信息

Department of Neurosurgery, the First Affiliated Hospital of Medical College, Shihezi University, Shihezi 832000, China.

Department of Neuromedicine, Beitun Hospital, the Tenth Division of Xinjiang Production and Construction Corps, Beitun 836000, China.

出版信息

J Stroke Cerebrovasc Dis. 2023 Dec;32(12):107391. doi: 10.1016/j.jstrokecerebrovasdis.2023.107391. Epub 2023 Oct 11.

DOI:10.1016/j.jstrokecerebrovasdis.2023.107391
PMID:37832268
Abstract

OBJECTIVES

This study explored the anti-inflammatory, anti-neuronal apoptosis, and neuroprotective effects of Neuritin in rat models of acute ischemia stroke (AIS).

METHODS

AIS was induced in male Sprague Dawley rats by middle cerebral artery occlusion (MCAO). Rats were divided into sham, MCAO, MCAO+neuritin, MCAO + neuritin + PBS, MCAO + neuritin+MCC950, and MCAO + neuritin + MSU groups. Neurological score assessment, brain water content measurement, HE staining, TTC staining, TUNEL staining, ELISA, and Western blot were performed.

RESULTS

Neuritin significantly improved the neurobehavioral score, infarct size, brain water content, apoptosis, and neuroinflammatory response compared with the MCAO and MCAO + PBS groups within 24 h after AIS. Moreover, Neuritin inhibited the protein expression of NLRP3 inflammasome, and reduced the expression of IL-18 and IL-1B, thereby reducing the inflammatory response. Meanwhile, the neuroprotection, anti-inflammation, and anti-apoptosis effects of Neuritin were enhanced by MCC950 but partly counteracted by MSU.

CONCLUSION

Neuritin may reduce brain injury after AIS by inhibiting the expression of NLRP3 inflammasome and then inhibiting the inflammatory response.

摘要

目的

本研究旨在探讨神经调节素(Neuritin)在大鼠急性缺血性脑卒中(AIS)模型中的抗炎、抗神经元凋亡和神经保护作用。

方法

通过大脑中动脉闭塞(MCAO)诱导雄性 Sprague Dawley 大鼠发生 AIS。将大鼠分为假手术组、MCAO 组、MCAO+Neuritin 组、MCAO+Neuritin+PBS 组、MCAO+Neuritin+MCC950 组和 MCAO+Neuritin+MSU 组。进行神经功能评分评估、脑水含量测量、HE 染色、TTC 染色、TUNEL 染色、ELISA 和 Western blot 分析。

结果

与 MCAO 组和 MCAO+PBS 组相比,Neuritin 能显著改善 AIS 后 24 h 内的神经行为评分、梗死面积、脑水含量、细胞凋亡和神经炎症反应。此外,Neuritin 抑制 NLRP3 炎性小体的蛋白表达,降低白细胞介素-18(IL-18)和白细胞介素-1β(IL-1β)的表达,从而减轻炎症反应。同时,MCC950 增强了 Neuritin 的神经保护、抗炎和抗凋亡作用,但 MSU 部分拮抗了这些作用。

结论

Neuritin 可能通过抑制 NLRP3 炎性小体的表达,从而抑制炎症反应,减轻 AIS 后的脑损伤。

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