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基于定量蛋白质组学质谱法分析GLP-1受体激动剂肽对脑缺血再灌注损伤的神经保护作用

Analysis of the neuroprotective effect of GLP-1 receptor agonist peptide on cerebral ischemia-reperfusion injury by Quantitative Proteomics Mass Spectrometry.

作者信息

Li Ying, Gong Min

机构信息

Tianjin Neurological Institute, Tianjin Medical University General Hospital, China.

Department of Pharmacy, Tianjin Medical University, Tianjin, China.

出版信息

Brain Behav. 2021 Jun;11(6):e02190. doi: 10.1002/brb3.2190. Epub 2021 May 21.

Abstract

OBJECTIVE

The pathological characteristics of cerebral ischemia-reperfusion injury (CIRI) are complex, and the mechanism involved remains unknown. The treatment for CIRI has become an increasingly important challenge in the clinic, prompting us to explore the mechanism of CIRI. It was reported that GLP-1 receptor agonist, Liraglutide, exhibited alleviating effects on CIRI. The previous findings suggested that the administration of Liraglutide in rodents results in the attenuation of the infarct volume following ischemia-reperfusion injury by mediating the reactive oxygen species, apoptotic and necroptotic pathways.

METHODS

Here, a proteomic study was performed aiming to clarify the physiological protection role of GLP-1 receptor agonist during the development of CIRI in MCAO mice. This proteomic investigations is contributed to reveal the mechanism associated with the treatment of GLP-1 receptor agonist in MCAO mice.

RESULTS

The results indicated that the occurrence of ischemia-reperfusion led to complex pathological processes, including inflammation, necroptosis and apoptosis. The treatment of Liraglutide significantly reduced the infract volume resulted from ischemia reperfusion injury. The proteomic data revealed that the administration of Liraglutide in MCAO mice induced the various effects on proteins expression level and phosphorylation.

CONCLUSIONS

The findings in this study was beneficial for identifying the novel therapeutic target for the treatment of ischemia reperfusion.

摘要

目的

脑缺血再灌注损伤(CIRI)的病理特征复杂,其涉及的机制尚不清楚。CIRI的治疗已成为临床上日益重要的挑战,促使我们探索CIRI的机制。据报道,胰高血糖素样肽-1(GLP-1)受体激动剂利拉鲁肽对CIRI具有缓解作用。先前的研究结果表明,在啮齿动物中给予利拉鲁肽可通过介导活性氧、凋亡和坏死性凋亡途径减轻缺血再灌注损伤后的梗死体积。

方法

在此,进行了一项蛋白质组学研究,旨在阐明GLP-1受体激动剂在大脑中动脉闭塞(MCAO)小鼠CIRI发生过程中的生理保护作用。这项蛋白质组学研究有助于揭示与GLP-1受体激动剂治疗MCAO小鼠相关的机制。

结果

结果表明,缺血再灌注的发生导致了复杂的病理过程,包括炎症、坏死性凋亡和凋亡。利拉鲁肽治疗显著减少了缺血再灌注损伤导致的梗死体积。蛋白质组学数据显示,在MCAO小鼠中给予利拉鲁肽对蛋白质表达水平和磷酸化产生了多种影响。

结论

本研究的结果有助于确定缺血再灌注治疗的新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d075/8213929/5cfe441ad46e/BRB3-11-e02190-g003.jpg

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