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基于 TMT 和 PRM 的定量蛋白质组学探索鸢尾苷 B 在中风中的保护作用和机制。

TMT and PRM Based Quantitative Proteomics to Explore the Protective Role and Mechanism of Iristectorin B in Stroke.

机构信息

College of Life Sciences, Changchun Normal University, Changchun 130032, China.

Central Laboratory, Changchun Normal University, Changchun 130032, China.

出版信息

Int J Mol Sci. 2023 Oct 15;24(20):15195. doi: 10.3390/ijms242015195.

Abstract

Stroke is a serious disease caused by the rupture or blockage of the cerebrovascular system. Its pathogenesis is complex and involves multiple mechanisms. Iristectorin B is a natural isoflavone that has certain anti stroke effects. In this study, an in vitro stroke injury model of glyoxylate deprivation was established using PC12 cells, which was used to evaluate the anti-stroke activity of Iristectorin B in ejecta stem. The results showed that Iristectorin B, a natural isoflavone derived from Dried Shoot, significantly reduced the damage to PC12 cells caused by oxygen glucose deprivation/reoxygenation, decreased apoptosis, enhanced cell survival and reduced Ca, LDH and ROS levels. The results showed that Iristectorin B had a significant protective effect on NaSO-injured PC12 cells, and the mechanism may be related to the protective effect of neurons in the brain. After protein extraction and various analyses were performed, a series of cutting-edge technologies were organically combined to study the quantitative proteome of each group. Differential proteins were then analyzed. According to the protein screening principle, ferroptosis-related proteins were most closely associated with stroke. The differential proteins associated with ferroptosis screened were SLC3A2, TFR1 and HMOX1, with HMOX1 being the most significantly elevated and reduced via dosing. Iristectorin B may act as a protective agent against stroke by regulating ferroptosis, and SLC3A2, TFR1 and HMOX1 may serve as potential diagnostic biomarkers for stroke, providing additional evidence to support the importance of ferroptosis in stroke.

摘要

中风是一种由脑血管系统破裂或阻塞引起的严重疾病。其发病机制复杂,涉及多种机制。鸢尾黄素 B 是一种天然异黄酮,具有一定的抗中风作用。本研究采用 PC12 细胞建立了乙醛酸剥夺体外中风损伤模型,用于评价鸢尾黄素 B 在脑溢片中的抗中风活性。结果表明,鸢尾黄素 B 可显著减轻氧葡萄糖剥夺/再氧合引起的 PC12 细胞损伤,减少细胞凋亡,提高细胞存活率,降低 Ca、LDH 和 ROS 水平。结果表明,鸢尾黄素 B 对 NaSO 损伤的 PC12 细胞具有显著的保护作用,其机制可能与脑神经元的保护作用有关。经过蛋白质提取和各种分析后,将一系列前沿技术有机结合,研究了每组的定量蛋白质组。然后分析差异蛋白。根据蛋白质筛选原则,与中风最密切相关的是铁死亡相关蛋白。筛选出的与铁死亡相关的差异蛋白有 SLC3A2、TFR1 和 HMOX1,其中 HMOX1 经剂量处理后升高和降低最显著。鸢尾黄素 B 可能通过调节铁死亡来发挥抗中风作用,SLC3A2、TFR1 和 HMOX1 可能成为中风的潜在诊断生物标志物,为铁死亡在中风中的重要性提供了更多证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a73/10607092/3e70dbd2d4e8/ijms-24-15195-g001.jpg

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