Ji Chengyuan, Cheng Dejing, Yang Siyuan, Wang Zhong
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu,215000, China.
Department of Rehabilitation Medicine, The Fourth Affiliated Hospital of Soochow University, Suzhou, Jiangsu,215000, China.
Iran J Biotechnol. 2025 Jan 1;23(1). doi: 10.30498/ijb.2025.487125.4019. eCollection 2025 Jan.
Intracerebral hemorrhage (ICH) is an extremely common acute vascular disease in the elderly population with a high potential for disability and death.
To analyze TYROBP related to blood-brain barrier (BBB) function in ICH through online databases, and to explore their mechanisms of action.
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.
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.
TYROBP promotes the pathological progression of ICH by increasing the BBB permeability and facilitating microglial pyroptosis.
脑出血（ICH）是老年人群中极为常见的急性血管疾病，具有较高的致残和致死风险。
通过在线数据库分析脑出血中与血脑屏障（BBB）功能相关的TYROBP，并探讨其作用机制。
选择GSE24265数据集进行GEO2R分析，随后进行基因本体论（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，验证脑出血中TYROBP的表达。构建TYROBP表达异常的慢病毒载体并干预脑出血大鼠。通过莫里斯水迷宫试验测试大鼠的认知和学习能力，并检测脑组织的病理损伤、炎症反应和氧化应激反应。最后，评估大鼠的血脑屏障和小胶质细胞焦亡情况。
对GSE24265数据集的分析显示TYROBP上调，在脑出血大鼠中也升高。增强TYROBP表达后，脑出血大鼠的学习和认知能力进一步恶化，脑组织的病理损伤加重，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。
TYROBP通过增加血脑屏障通透性和促进小胶质细胞焦亡促进脑出血的病理进展。
