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炎症相关基因和血清 microRNAs 在青年缺血性脑卒中的不同表达模式。

Different expression patterns of inflammation-related genes and serum microRNAs in young-onset ischemic stroke.

机构信息

Department of Neurology and Neurosurgery, University of Tartu, L. Puusepa 8, 50406, Tartu, Estonia.

Department of Biomedicine, University of Tartu, Tartu, Estonia.

出版信息

Sci Rep. 2024 Oct 11;14(1):23845. doi: 10.1038/s41598-024-74995-0.

Abstract

Brain ischemia results in the activation of a cascade of inflammatory responses, contributing to the pathogenesis of stroke. This study aimed to assess the patterns of possible changes in the expression of specific inflammation-associated protein-encoding genes and miRNAs in the peripheral blood between the acute and chronic phase of young-onset cryptogenic (Cryp) and large-artery atherosclerotic (LAA) stroke. Blood and serum were collected from patients with cryptogenic and large-artery atherosclerotic stroke at the stroke onset and 1-year follow-up. The relative expression of inflammation-related genes was analysed at the mRNA and miRNA levels using real-time quantitative PCR. Moreover, the relationship between the relative gene expression levels and clinical data was assessed using several different statistical approaches. Seventy-three patients were included in this study, with a median age of 47 (IQR, 9) years. Approximately 72% were men. In patients with cryptogenic stroke, at the mRNA level, ICAM1, CXCL8, TNF, NFKBIA, PYCARD, IL1B, and IL18 were observed to be upregulated at the stroke onset compared to the 1-year follow-up. In patients with LAA stroke, only the expression of NFKBIA was significantly higher during acute stroke. Further, the miRNA serum levels of miR-21, miR-122, and miR-155 were higher at the onset of stroke in patients with cryptogenic stroke but not in those with LAA stroke. The differences between the relative gene expression levels during acute stroke and at the 1-year follow-up were more pronounced in patients with cryptogenic stroke with no cardiovascular risk factors. The expression changes of inflammatory genes in whole blood and miRNAs in the serum differ in patients with cryptogenic and LAA stroke.

摘要

脑缺血导致炎症反应级联激活,导致中风发病机制。本研究旨在评估年轻起病的隐源性(Cryp)和大动脉粥样硬化性(LAA)中风患者在急性和慢性期外周血中特定炎症相关蛋白编码基因和 miRNA 表达可能发生的变化模式。在中风发作时和 1 年随访时,从隐源性和大动脉粥样硬化性中风患者中采集血液和血清。使用实时定量 PCR 分析炎症相关基因在 mRNA 和 miRNA 水平上的相对表达。此外,还使用几种不同的统计方法评估了相对基因表达水平与临床数据之间的关系。本研究共纳入 73 例患者,中位年龄为 47(IQR,9)岁。约 72%为男性。在隐源性中风患者中,与 1 年随访相比,ICAM1、CXCL8、TNF、NFKBIA、PYCARD、IL1B 和 IL18 在中风发作时 mRNA 水平上调。在 LAA 中风患者中,仅 NFKBIA 在急性中风时表达明显升高。此外,在隐源性中风患者中,miR-21、miR-122 和 miR-155 的血清 miRNA 水平在中风发作时较高,但在 LAA 中风患者中则不然。在无心血管危险因素的隐源性中风患者中,急性中风和 1 年随访时相对基因表达水平的差异更为明显。全血中炎症基因的表达变化和血清中 miRNA 的表达在隐源性和 LAA 中风患者中不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c15/11470008/7b0dbd298b27/41598_2024_74995_Fig1_HTML.jpg

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