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自发性高血压大鼠海马组织在急性低压缺氧暴露下的转录组学分析:与炎症和能量代谢的关联。

Transcriptomic analysis of the cerebral hippocampal tissue in spontaneously hypertensive rats exposed to acute hypobaric hypoxia: associations with inflammation and energy metabolism.

机构信息

Center for Aerospace Clinical Medicine, Department of Aerospace Medicine, Air Force Medical University, Xi'an, 710032, China.

Department of Military Medical Equipment and Metrology, School of Military Biomedical Engineering, Air Force Medical University, Xi'an, 710032, China.

出版信息

Sci Rep. 2023 Mar 6;13(1):3681. doi: 10.1038/s41598-023-30682-0.

Abstract

We evaluated the effect of acute hypobaric hypoxia (AHH) on the hippocampal region of the brain in early-stage spontaneously hypertensive male rats. The rats were classified into a control (ground level; ~ 400 m altitude) group and an AHH experimental group placed in an animal hypobaric chamber at a simulated altitude of 5500 m for 24 h. RNA-Seq analysis of the brains and hippocampi showed that differentially expressed genes (DEGs) were primarily associated with ossification, fibrillar collagen trimer, and platelet-derived growth factor binding. The DEGs were classified into functional categories including general function prediction, translation, ribosomal structure and biogenesis, replication, recombination, and repair. Pathway enrichment analysis revealed that the DEGs were primarily associated with relaxin signaling, PI3K-Akt signaling, and amoebiasis pathways. Protein-protein interaction network analysis indicated that 48 DEGs were involved in both inflammation and energy metabolism. Further, we performed validation experiments to show that nine DEGs were closely associated with inflammation and energy metabolism, of which two (Vegfa and Angpt2) and seven (Acta2, Nfkbia, Col1a1, Edn1, Itga1, Ngfr, and Sgk1) genes showed up and downregulated expression, respectively. Collectively, these results indicated that inflammation and energy metabolism-associated gene expression in the hippocampus was altered in early-stage hypertension upon AHH exposure.

摘要

我们评估了急性低压缺氧(AHH)对早期自发性高血压雄性大鼠海马区的影响。这些大鼠被分为对照组(地面水平;~400 米海拔)和 AHH 实验组,实验组被放置在动物低压舱中,模拟海拔 5500 米的环境中 24 小时。大脑和海马的 RNA-Seq 分析表明,差异表达基因(DEGs)主要与骨化、纤维胶原三聚体和血小板衍生生长因子结合有关。DEGs 被分类为功能类别,包括一般功能预测、翻译、核糖体结构和生物发生、复制、重组和修复。通路富集分析表明,DEGs 主要与松弛素信号、PI3K-Akt 信号和变形虫病途径有关。蛋白质-蛋白质相互作用网络分析表明,48 个 DEGs 参与了炎症和能量代谢。此外,我们进行了验证实验,表明九个 DEGs 与炎症和能量代谢密切相关,其中两个(Vegfa 和 Angpt2)和七个(Acta2、Nfkbia、Col1a1、Edn1、Itga1、Ngfr 和 Sgk1)基因分别表现出上调和下调表达。综上所述,这些结果表明,在 AHH 暴露引起的早期高血压中,海马区与炎症和能量代谢相关的基因表达发生了改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac04/9988845/e0c5c31c18a8/41598_2023_30682_Fig1_HTML.jpg

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