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缺血性卒中中两种不同免疫浸润性细胞焦亡亚型的特征

Characteristics of two different immune infiltrating pyroptosis subtypes in ischemic stroke.

作者信息

Xiao Yilei, Wang Zhen, Xin Yexin, Wang Xingbang, Dong Zhaogang

机构信息

Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, 252000, Shangdong, China.

Department of Clinical Laboratory, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, 250012, Shandong, China.

出版信息

Heliyon. 2024 Aug 22;10(17):e36349. doi: 10.1016/j.heliyon.2024.e36349. eCollection 2024 Sep 15.

DOI:10.1016/j.heliyon.2024.e36349
PMID:39263102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11388774/
Abstract

BACKGROUND

Ischemic stroke (IS) is a serious health hazard and identified as the second leading cause of mortality around the world. However, the role of pyroptosis in the immune microenvironment regulation in IS is still unclear. Here, our study aims to elucidate the effect of pyroptosis on immune microenvironment in IS.

METHODS

The regulation mode of pyroptosis in IS was systematically evaluated, and its effects on immune microenvironment were explored, including infiltration of immune cells, immune response gene sets, and human leukocyte antigen (HLA) gene. The genes and drugs related to pyroptosis phenotype were also identified. An MCAO rat model was constructed, and the mRNA expression levels in the classifier model were validated by qRT-PCR.

RESULTS

The separator is composed of 11 pyroptosis genes, out of which 10 genes could distinguish between ischemic stroke and control samples. CHMP2A, CHMP4A, and NAIP genes are significantly related to immune infiltrating cells, immune response gene sets, and HLA. However, two different pyroptosis subtypes mediated by 10 pyroptosis genes were identified, which were different in immune cell abundance, HLA genes, and immune response gene sets. Furthermore, 199 genes associated with pyroptosis phenotype was identified along with the analysis of biological functions.

CONCLUSION

These findings reveal the potential mechanism of pyroptosis in the immune microenvironment of IS, indicating that pyroptosis functions as a vital component in the complexity and diversity of the immune microenvironment in patients with IS.

摘要

背景

缺血性中风(IS)是一种严重的健康危害,被确定为全球第二大死亡原因。然而,细胞焦亡在缺血性中风免疫微环境调节中的作用仍不清楚。在此,我们的研究旨在阐明细胞焦亡对缺血性中风免疫微环境的影响。

方法

系统评估缺血性中风中细胞焦亡的调节模式,并探讨其对免疫微环境的影响,包括免疫细胞浸润、免疫反应基因集和人类白细胞抗原(HLA)基因。还鉴定了与细胞焦亡表型相关的基因和药物。构建了大脑中动脉闭塞(MCAO)大鼠模型,并通过qRT-PCR验证分类模型中的mRNA表达水平。

结果

该分类器由11个细胞焦亡基因组成,其中10个基因可区分缺血性中风和对照样本。CHMP2A、CHMP4A和NAIP基因与免疫浸润细胞、免疫反应基因集和HLA显著相关。然而,鉴定出由10个细胞焦亡基因介导的两种不同的细胞焦亡亚型,它们在免疫细胞丰度、HLA基因和免疫反应基因集方面存在差异。此外,通过生物学功能分析鉴定出199个与细胞焦亡表型相关的基因。

结论

这些发现揭示了细胞焦亡在缺血性中风免疫微环境中的潜在机制,表明细胞焦亡在缺血性中风患者免疫微环境的复杂性和多样性中起着重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/67868e9db4d2/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/903d9b94da52/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/cfab4aa43071/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/c540c0d03788/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/65c1aa5661bb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/2b2a55e56fb4/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/07e01ee03d14/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/871f4fce59b3/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/67868e9db4d2/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/903d9b94da52/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/cfab4aa43071/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/c540c0d03788/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/65c1aa5661bb/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/2b2a55e56fb4/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/07e01ee03d14/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/871f4fce59b3/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ff2/11388774/67868e9db4d2/gr8.jpg

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本文引用的文献

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HIF-1, an important regulator in potential new therapeutic approaches to ischemic stroke.缺氧诱导因子-1(HIF-1),缺血性脑卒中潜在新型治疗方法的重要调控因子。
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