Zhou Chen-hui, Wang Chun-xi, Xie Guang-bin, Wu Ling-yun, Wei Yong-xiang, Wang Qiang, Zhang Hua-sheng, Hang Chun-hua, Zhou Meng-liang, Shi Ji-xin
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, China.
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, Jiangsu Province, China.
Brain Res. 2015 Dec 10;1629:250-9. doi: 10.1016/j.brainres.2015.10.016. Epub 2015 Oct 20.
Early brain injury (EBI) determines the unfavorable outcomes after subarachnoid hemorrhage (SAH). Fisetin, a natural flavonoid, has anti-inflammatory and neuroprotection properties in several brain injury models, but the role of fisetin on EBI following SAH remains unknown. Our study aimed to explore the effects of fisetin on EBI after SAH in rats. Adult male Sprague-Dawley rats were randomly divided into the sham and SAH groups, fisetin (25mg/kg or 50mg/kg) or equal volume of vehicle was given at 30min after SAH. Neurological scores and brain edema were assayed. The protein expression of toll-like receptor 4 (TLR 4), p65, ZO-1 and bcl-2 was examined by Western blot. TLR 4 and p65 were also assessed by immunohistochemistry (IHC). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the production of pro-inflammatory cytokines. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) was perform to assess neural cell apoptosis. High-dose (50mg/kg) fisetin significantly improved neurological function and reduced brain edema at both 24h and 72h after SAH. Remarkable reductions of TLR 4 expression and nuclear factor κB (NF-κB) translocation to nucleus were detected after fisetin treatment. In addition, fisetin significantly reduced the productions of pro-inflammatory cytokines, decreased neural cell apoptosis and increased the protein expression of ZO-1 and bcl-2. Our data provides the evidence for the first time that fisetin plays a protective role in EBI following SAH possibly by suppressing TLR 4/NF-κB mediated inflammatory pathway.
早期脑损伤（EBI）决定了蛛网膜下腔出血（SAH）后的不良预后。非瑟酮是一种天然黄酮类化合物，在多种脑损伤模型中具有抗炎和神经保护特性，但非瑟酮对SAH后EBI的作用尚不清楚。我们的研究旨在探讨非瑟酮对大鼠SAH后EBI的影响。成年雄性Sprague-Dawley大鼠随机分为假手术组和SAH组，SAH后30分钟给予非瑟酮（25mg/kg或50mg/kg）或等体积的溶媒。检测神经功能评分和脑水肿情况。通过蛋白质免疫印迹法检测Toll样受体4（TLR 4）、p65、紧密连接蛋白1（ZO-1）和bcl-2的蛋白表达。还通过免疫组织化学（IHC）评估TLR 4和p65。采用酶联免疫吸附测定（ELISA）检测促炎细胞因子的产生。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）评估神经细胞凋亡。高剂量（50mg/kg）非瑟酮在SAH后24小时和72小时均显著改善神经功能并减轻脑水肿。非瑟酮治疗后检测到TLR 4表达和核因子κB（NF-κB）向细胞核的转位显著减少。此外，非瑟酮显著降低促炎细胞因子的产生，减少神经细胞凋亡，并增加ZO-1和bcl-2的蛋白表达。我们的数据首次证明非瑟酮可能通过抑制TLR 4/NF-κB介导的炎症途径在SAH后的EBI中发挥保护作用。
