Zheng Bao, Zhou Xiwei, Pang Lujun, Che Yanjun, Qi Xin
Department of Neurosurgery, Jingjiang People's Hospital, Jingjiang, China.
J Biochem Mol Toxicol. 2025 Jan;39(1):e70099. doi: 10.1002/jbt.70099.
Subarachnoid hemorrhage (SAH) is a specific type of stroke. Dihydroquercetin (DHQ), a flavonoid, is known for its various pharmacological properties. This study aimed to explore the roles and mechanisms of DHQ in influencing the progression of SAH. A rat SAH model was established using the endovascular perforation technique. Following SAH induction, DHQ was administered orally 1 h later. Assessments included SAH scores, neurological function, brain swelling, blood-brain barrier (BBB) integrity, neuronal damage, apoptosis levels, inflammation, and indicators of ferroptosis using various treatments. The HT22 cells were exposed to hemin to simulate SAH-like conditions under in vitro settings. Cell counting kit-8 assays, flow cytometry, enzyme?linked immunosorbent assay, BODIPY 581/591 C11 staining, western blot analysis, and biochemical kits were employed to evaluate the potential effects of DHQ. Moreover, the mechanisms responsible for the protective effect of DHQ were examined by western blot analysis. The in vivo findings revealed that DHQ mitigated neurological impairments, brain swelling, BBB disruption, and neuronal injury at 24 h post-SAH. DHQ also reduced neuronal degeneration, inflammation, and ferroptosis following SAH. The in vitro findings revealed that DHQ enhanced cell survival and reduced ferroptosis at 24 h following hemin exposure. Mechanistically, DHQ activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in SAH rats and hemin-treated HT22 cells to exert neuroprotective effects. In conclusion, this study reveals that DHQ can effectively decrease BBB permeability, brain edema, neurological dysfunctions, and ferroptosis post-SAH by activating the PI3K/AKT/Nrf2/HO-1 pathway.
蛛网膜下腔出血（SAH）是一种特殊类型的中风。二氢槲皮素（DHQ）是一种黄酮类化合物，以其多种药理特性而闻名。本研究旨在探讨DHQ在影响SAH进展中的作用和机制。采用血管内穿刺技术建立大鼠SAH模型。SAH诱导后1小时口服给予DHQ。使用各种处理方法进行评估，包括SAH评分、神经功能、脑肿胀、血脑屏障（BBB）完整性、神经元损伤、细胞凋亡水平、炎症以及铁死亡指标。在体外环境中，将HT22细胞暴露于氯化血红素以模拟SAH样条件。采用细胞计数试剂盒-8检测、流式细胞术、酶联免疫吸附测定、BODIPY 581/591 C11染色、蛋白质免疫印迹分析和生化试剂盒来评估DHQ的潜在作用。此外，通过蛋白质免疫印迹分析研究了DHQ发挥保护作用的机制。体内研究结果显示，SAH后24小时，DHQ减轻了神经功能障碍、脑肿胀、BBB破坏和神经元损伤。DHQ还减少了SAH后的神经元变性、炎症和铁死亡。体外研究结果显示，氯化血红素处理24小时后，DHQ提高了细胞存活率并减少了铁死亡。机制上，DHQ激活了SAH大鼠和氯化血红素处理的HT22细胞中的磷脂酰肌醇-4,5-二磷酸3-激酶（PI3K）/蛋白激酶B（AKT）/核因子红细胞2相关因子2（Nrf2）信号通路，从而发挥神经保护作用。总之，本研究表明，DHQ可通过激活PI3K/AKT/Nrf2/HO-1通路有效降低SAH后的BBB通透性、脑水肿、神经功能障碍和铁死亡。
