Background. Intracerebral hemorrhage (ICH) is among the common types of stroke with high mortality and morbidity. Molecular biomarker selection is crucial for ICH diagnosis and treatment. However, the identification of ICH-related biomarkers remains inadequate. Materials and Methods. In vivo and in vitro ICH models were generated and transfected with silenced B-cell lymphoma-3 (BCL-3 and siRNA BCL-3), overexpressed BCL-3, and endoplasmic reticulum stress (ERS) agonist (2-CLHA). Hematoxylin–eosin staining and transmission electron microscopy were used to observe the transfected cells. RNA sequencing was performed in vivo on the sham and ICH groups. The blood–brain barrier (BBB) permeability was evaluated by determining Evans blue dye extravasation, transendothelial electrical resistance, and paracellular permeability. Moreover, tight junction-, cell apoptosis-, and endoplasmic reticulum stress- (ERS-) related proteins were evaluated through real-time quantitative PCR, western blotting, immunohistochemistry, and TUNEL staining. The levels of inflammatory cytokines were measured through the enzyme-linked immunosorbent assay. Results. RNA-seq revealed that BCL-3 acts as a key player. BCL-3 promotes ICH progression by increasing BBB permeability, ERS, inflammation, and cell apoptosis. Silencing of BCL-3 slows ICH progression by reducing BBB permeability and inflammation and terminating cell apoptosis and ERS in vitro and in vivo. Conclusion. Our study identified ICH biomarkers and elucidated the role of BCL-3 in ICH for the first time.

中文翻译：

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BCL-3 通过内质网应激增加血脑屏障通透性、炎症和细胞凋亡，从而促进脑出血进展

背景。脑出血（ICH）是常见的卒中类型之一，死亡率和发病率较高。分子生物标志物的选择对于ICH的诊断和治疗至关重要。然而，ICH相关生物标志物的鉴定仍然不足。材料和方法。生成体内和体外ICH 模型，并用沉默的 B 细胞淋巴瘤 3（BCL-3 和 siRNA BCL-3）、过表达的 BCL-3 和内质网应激 (ERS) 激动剂 (2-CLHA) 转染。采用苏木精-伊红染色和透射电镜观察转染细胞。对假手术组和 ICH 组进行体内RNA 测序。通过测定伊文思蓝染料外渗、跨内皮电阻和细胞旁通透性来评估血脑屏障（BBB）通透性。此外，通过实时定量 PCR、蛋白质印迹、免疫组织化学和 TUNEL 染色评估紧密连接、细胞凋亡和内质网应激 (ERS) 相关蛋白。通过酶联免疫吸附测定测定炎症细胞因子的水平。结果。RNA-seq 揭示 BCL-3 发挥着关键作用。BCL-3 通过增加 BBB 通透性、ERS、炎症和细胞凋亡来促进 ICH 进展。在体外和体内，BCL-3 的沉默可通过降低 BBB 通透性和炎症以及终止细胞凋亡和 ERS ​​来减缓 ICH 进展。结论。我们的研究首次鉴定了 ICH 生物标志物并阐明了 BCL-3 在 ICH 中的作用。