Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, 1 Friendship Road, 400016 Chongqing, China.
Exp Neurol. 2012 Dec;238(2):218-24. doi: 10.1016/j.expneurol.2012.08.025. Epub 2012 Aug 28.
Endothelial apoptosis plays a major role in the development of cerebral vascular spasm after subarachnoid hemorrhage (SAH). C/EBP homologous protein (CHOP) orchestrates apoptosis in a variety of cell types in response to endoplasmic reticulum (ER) stress, implicated in the brain injury after SAH. However, the role of CHOP in the mechanism of cerebral vasospasm (CVS) after SAH remains unexplored. The aim of this study was to evaluate the effect of CHOP silencing on endothelial apoptosis and CVS following subarachnoid hemorrhage in the rat. The study was conducted on 65 rats and employed endovascular perforation model of SAH. CHOP siRNAs were injected 24 h prior to the hemorrhage. At 72 h after SAH brains with basilar arteries (BA) were collected from euthanized rats for laboratory investigations. Triple fluorescence stain revealed expression of CHOP in cerebral vascular endothelia after SAH. Marked reduction of CHOP protein and the reduction of its downstream signaling effectors, bim and caspase-3, were found in BA with Western blot analysis. CHOP silencing reduced number of apoptotic endothelial cells in BA, and increased BA diameter after SAH. The amelioration of CVS was associated with reduced neuronal injury in cerebral tissues. In conclusion, CHOP siRNA treatment can effectively combat apoptotic mechanisms of cerebral vasospasm set in motion by subarachnoid bleeding.
内皮细胞凋亡在蛛网膜下腔出血（SAH）后脑血管痉挛的发展中起主要作用。C/EBP 同源蛋白（CHOP）在各种细胞类型中通过内质网（ER）应激协调细胞凋亡，与 SAH 后的脑损伤有关。然而，CHOP 在 SAH 后血管痉挛（CVS）机制中的作用仍未被探索。本研究旨在评估 CHOP 沉默对蛛网膜下腔出血后大鼠内皮细胞凋亡和 CVS 的影响。该研究在 65 只大鼠上进行，并采用了蛛网膜下腔出血的血管内穿孔模型。CHOP siRNA 在出血前 24 小时注射。在 SAH 后 72 小时，从安乐死大鼠中收集带有基底动脉（BA）的大脑进行实验室研究。三重荧光染色显示 CHOP 在 SAH 后存在于脑血管内皮细胞中。Western blot 分析显示，BA 中 CHOP 蛋白及其下游信号效应物 bim 和 caspase-3 的表达明显减少。CHOP 沉默减少了 BA 中凋亡的内皮细胞数量，并增加了 SAH 后的 BA 直径。CVS 的改善与脑组织中神经元损伤的减少有关。总之，CHOP siRNA 治疗可以有效地对抗由蛛网膜下腔出血引发的血管痉挛的凋亡机制。
