Validation of the Mechanism of Action of TYROBP Related to Blood-Brain Barrier Function in Intracerebral Hemorrhage by Bioinformatics Analysis.

IF 1.6 4区 生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Chengyuan Ji, Dejing Cheng, Siyuan Yang, Zhong Wang
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Abstract

Background: Intracerebral hemorrhage (ICH) is an extremely common acute vascular disease in the elderly population with a high potential for disability and death.

Objective: To analyze TYROBP related to blood-brain barrier (BBB) function in ICH through online databases, and to explore their mechanisms of action.

Materials and methods: The GSE24265 dataset was chosen for GEO2R analysis, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. It was discovered that TYROBP was related to the "maintenance of permeability of BBB". Subsequently, ICH rat models were constructed, and TYROBP expression in ICH was verified. Lentivirus vectors with abnormally expressed TYROBP were constructed and intervened in ICH rats. The cognitive and learning abilities of rats were tested by the Morris water maze test, and the pathological damage, inflammatory reactions, and oxidative stress responses of brain tissue were detected. Finally, the BBB and microglial pyroptosis in rats were evaluated.

Results: Analysis of the GSE24265 dataset showed upregulation of TYROBP, which was also elevated in ICH rats. After enhancing TYROBP expression, the learning and cognitive abilities of ICH rats were further deteriorated, the pathological damage of brain tissues was aggravated, and the BBB leakage and microglial pyroptosis were intensified; silencing TYROBP expression led to completely reversed pathological processes.

Conclusions: TYROBP promotes the pathological progression of ICH by increasing the BBB permeability and facilitating microglial pyroptosis.

用生物信息学分析验证TYROBP在脑出血中与血脑屏障功能相关的作用机制。
背景:脑出血是老年人中一种极为常见的急性血管疾病,具有致残和死亡的高危险性。目的:通过在线数据库分析与脑出血血脑屏障(BBB)功能相关的TYROBP,并探讨其作用机制。材料和方法:选择GSE24265数据集进行GEO2R分析,然后进行基因本体(GO)和京都基因与基因组百科全书(KEGG)功能富集分析。发现TYROBP与“血脑屏障通透性的维持”有关。随后,构建脑出血大鼠模型,验证TYROBP在脑出血中的表达。构建异常表达TYROBP的慢病毒载体,对脑出血大鼠进行干预。采用Morris水迷宫实验检测大鼠的认知和学习能力,并检测脑组织病理损伤、炎症反应和氧化应激反应。最后对大鼠血脑屏障和小胶质细胞焦亡进行评价。结果:对GSE24265数据集的分析显示TYROBP上调,在ICH大鼠中也升高。TYROBP表达增强后,脑出血大鼠的学习和认知能力进一步恶化,脑组织病理损伤加重,血脑屏障渗漏和小胶质细胞焦亡加剧;沉默TYROBP表达导致病理过程完全逆转。结论:TYROBP通过增加血脑屏障通透性,促进小胶质细胞焦亡,促进脑出血病理进展。
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来源期刊
Iranian Journal of Biotechnology
Iranian Journal of Biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-
CiteScore
2.60
自引率
7.70%
发文量
20
期刊介绍: Iranian Journal of Biotechnology (IJB) is published quarterly by the National Institute of Genetic Engineering and Biotechnology. IJB publishes original scientific research papers in the broad area of Biotechnology such as, Agriculture, Animal and Marine Sciences, Basic Sciences, Bioinformatics, Biosafety and Bioethics, Environment, Industry and Mining and Medical Sciences.
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