Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Sci Rep. 2017 Mar 22;7:44918. doi: 10.1038/srep44918.
Early brain injury following subarachnoid hemorrhage (SAH) strongly determines the prognosis of patients suffering from an aneurysm rupture, and apoptosis is associated with early brain injury after SAH. This study was designed to explore the role of X-linked inhibitor of apoptosis (XIAP) in early brain injury following SAH. The expression of XIAP was detected using western blotting and real-time RT-PCR in an autologous blood injection model of SAH. We also studied the role of XIAP in early brain injury and detected apoptosis-related proteins. The results showed that XIAP was significantly up-regulated in the cortex and hippocampus and that XIAP was mainly expressed in neuronal cells following SAH. The inhibition of endogenous XIAP aggravated blood-brain barrier disruption, neurological deficits and brain edema. Recombinant XIAP preserved the blood-brain barrier, improved the neurological scores and ameliorated brain edema. Recombinant XIAP treatment also decreased the expression of cleaved caspase-3, caspase-8 and caspase-9, whereas there was no effect on the expression of p53, apoptosis-inducing factor or cytochrome c. These results show that XIAP acts as an endogenous neuroprotective and anti-apoptotic agent following SAH. The effects of XIAP on early brain injury was associated with the inhibition of the caspase-dependent apoptosis pathway.
蛛网膜下腔出血 (SAH) 后的早期脑损伤强烈决定了动脉瘤破裂患者的预后，而细胞凋亡与 SAH 后的早期脑损伤有关。本研究旨在探讨凋亡抑制蛋白 (XIAP) 在蛛网膜下腔出血后早期脑损伤中的作用。采用自体血注入 SAH 模型，通过 Western blot 和实时 RT-PCR 检测 XIAP 的表达。我们还研究了 XIAP 在早期脑损伤中的作用，并检测了凋亡相关蛋白。结果表明，XIAP 在皮层和海马区明显上调，SAH 后 XIAP 主要在神经元细胞中表达。内源性 XIAP 的抑制加重了血脑屏障的破坏、神经功能缺损和脑水肿。重组 XIAP 可保护血脑屏障，改善神经评分，减轻脑水肿。重组 XIAP 治疗还降低了 cleaved caspase-3、caspase-8 和 caspase-9 的表达，但对 p53、凋亡诱导因子或细胞色素 c 的表达没有影响。这些结果表明，XIAP 在 SAH 后作为一种内源性神经保护和抗细胞凋亡因子发挥作用。XIAP 对早期脑损伤的影响与抑制 caspase 依赖性细胞凋亡途径有关。
