Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis.

IF 1.7 4区医学 Q2 MEDICINE, GENERAL & INTERNAL

Open Medicine Pub Date : 2024-11-04 eCollection Date: 2024-01-01 DOI:10.1515/med-2024-1063

Fei Yu, Guangxue Wang, Xingyi Chen, Yanfei Zhang, Cheng Yang, Hui Hu, Liang Wei

{"title":"Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis.","authors":"Fei Yu, Guangxue Wang, Xingyi Chen, Yanfei Zhang, Cheng Yang, Hui Hu, Liang Wei","doi":"10.1515/med-2024-1063","DOIUrl":null,"url":null,"abstract":"Objective: This study aimed to clarify the roles and underlying mechanisms of luteolin in the progression of cerebral ischemia/reperfusion injury (CIRI).Methods: A mouse model of CIRI was established using the middle cerebral artery occlusion (MCAO) method, after which luteolin was administered. Subsequently, neuronal apoptosis and pyroptosis were measured and the brain tissues of each group were subjected to RNA sequencing.Results: Luteolin alleviated MCAO-induced brain infarction, apoptosis, and pyroptosis. RNA sequencing identified 3,379, 2,777, and 3,933 differentially expressed genes (DEGs) in the MCAO vs sham, MCAO vs MCAO + luteolin, and MCAO + luteolin vs sham groups, respectively. The identified DEGs showed enrichment in multiple processes, including pattern specification, forebrain development, anion transport, leukocyte migration, regulation of cell-cell adhesion, and positive regulation of the response to external stimuli, as well as the calcium, PI3K-AKT, JAK-STAT, NF-kappa B, IL-17, cAMP, cGMP-PKG, and Wnt signaling pathways. In addition, Ccl2 and Angpt2 interacted more with the other top 30 DEGs with high interaction weights. Finally, RT-qPCR results showed that MCAO induction significantly up-regulated the expression of Stoml3, Eomes, and Ms4a15 and down-regulated Nms, Ttr, and Avpr1a; however, luteolin could partially reverse the expression caused by MCAO.Conclusion: Luteolin can alleviate brain infarction, apoptosis, and pyroptosis in CIRI, and may improve MCAO-induced CIRI by targeting the identified DEGs and their enriched pathways.","PeriodicalId":19715,"journal":{"name":"Open Medicine","volume":"19 1","pages":"20241063"},"PeriodicalIF":1.7000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538924/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Open Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1515/med-2024-1063","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: This study aimed to clarify the roles and underlying mechanisms of luteolin in the progression of cerebral ischemia/reperfusion injury (CIRI).

Methods: A mouse model of CIRI was established using the middle cerebral artery occlusion (MCAO) method, after which luteolin was administered. Subsequently, neuronal apoptosis and pyroptosis were measured and the brain tissues of each group were subjected to RNA sequencing.

Results: Luteolin alleviated MCAO-induced brain infarction, apoptosis, and pyroptosis. RNA sequencing identified 3,379, 2,777, and 3,933 differentially expressed genes (DEGs) in the MCAO vs sham, MCAO vs MCAO + luteolin, and MCAO + luteolin vs sham groups, respectively. The identified DEGs showed enrichment in multiple processes, including pattern specification, forebrain development, anion transport, leukocyte migration, regulation of cell-cell adhesion, and positive regulation of the response to external stimuli, as well as the calcium, PI3K-AKT, JAK-STAT, NF-kappa B, IL-17, cAMP, cGMP-PKG, and Wnt signaling pathways. In addition, Ccl2 and Angpt2 interacted more with the other top 30 DEGs with high interaction weights. Finally, RT-qPCR results showed that MCAO induction significantly up-regulated the expression of Stoml3, Eomes, and Ms4a15 and down-regulated Nms, Ttr, and Avpr1a; however, luteolin could partially reverse the expression caused by MCAO.

Conclusion: Luteolin can alleviate brain infarction, apoptosis, and pyroptosis in CIRI, and may improve MCAO-induced CIRI by targeting the identified DEGs and their enriched pathways.

查看原文本刊更多论文

木犀草素通过调节细胞热解减轻脑缺血再灌注损伤

研究目的本研究旨在阐明叶黄素在脑缺血再灌注损伤（CIRI）进展过程中的作用及其内在机制：方法：采用大脑中动脉闭塞法（MCAO）建立了一个CIRI小鼠模型，然后给小鼠服用叶黄素。方法：采用大脑中动脉闭塞（MCAO）法建立 CIRI 小鼠模型，然后给小鼠注射木犀草素，随后测定神经元凋亡和热凋亡，并对每组小鼠的脑组织进行 RNA 测序：结果：木犀草素可减轻 MCAO 诱导的脑梗塞、神经细胞凋亡和裂解。RNA 测序在 MCAO vs 假组、MCAO vs MCAO + 叶黄素组和 MCAO + 叶黄素 vs 假组中分别发现了 3,379 个、2,777 个和 3,933 个差异表达基因（DEGs）。所发现的DEGs富集于多个过程，包括模式分化、前脑发育、阴离子转运、白细胞迁移、细胞-细胞粘附调控、对外部刺激反应的正向调控，以及钙、PI3K-AKT、JAK-STAT、NF-kappa B、IL-17、cAMP、cGMP-PKG和Wnt信号通路。此外，Ccl2 和 Angpt2 与其他前 30 个 DEGs 的相互作用权重较高。最后，RT-qPCR结果显示，MCAO诱导可显著上调Stoml3、Eomes和Ms4a15的表达，下调Nms、Ttr和Avpr1a的表达；然而，叶黄素可部分逆转MCAO引起的表达：结论：木犀草素能缓解 CIRI 中的脑梗塞、细胞凋亡和热蛋白沉积，并可通过靶向已识别的 DEGs 及其富集通路改善 MCAO 诱导的 CIRI。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Open Medicine Medicine-General Medicine

CiteScore

3.00

自引率

0.00%

发文量

153

审稿时长

20 weeks

期刊介绍： Open Medicine is an open access journal that provides users with free, instant, and continued access to all content worldwide. The primary goal of the journal has always been a focus on maintaining the high quality of its published content. Its mission is to facilitate the exchange of ideas between medical science researchers from different countries. Papers connected to all fields of medicine and public health are welcomed. Open Medicine accepts submissions of research articles, reviews, case reports, letters to editor and book reviews.