Cheng Gao, Wei Liu, Zhi-Dan Sun, Shi-Guang Zhao, Xiang-Zhen Liu
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang, PR China.
BMC Neurosci. 2009 Jan 21;10:7. doi: 10.1186/1471-2202-10-7.
Cerebral vasospasm (CVS) and early brain injury remain major causes of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH. This study was designed to explore apoptosis inhibiting effects of atorvastatin and its potential apoptotic signal pathway after SAH.
Preserving blood-brain-barrier permeability, decreasing brain edema, increasing neurological scores and ameliorating cerebral vasospasm were obtained after prophylactic use of atorvastatin. TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin. Apoptosis-related proteins P53, AIF and Cytochrome C were up-regulated after SAH, while they were not affected by atorvastatin. In addition, up-regulation of caspase-3 and caspase-8 after SAH was decreased by atorvastatin treatment both in mRNA and in protein levels.
The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.
脑血管痉挛（CVS）和早期脑损伤仍然是动脉瘤性蛛网膜下腔出血（SAH）后发病和死亡的主要原因。羟甲基戊二酰辅酶A还原酶抑制剂，也称为他汀类药物，具有神经保护作用并可改善SAH后的CVS。本研究旨在探讨阿托伐他汀对SAH后细胞凋亡的抑制作用及其潜在的凋亡信号通路。
预防性使用阿托伐他汀后，可保持血脑屏障通透性、减轻脑水肿、提高神经功能评分并改善脑血管痉挛。阿托伐他汀可使基底动脉和脑皮质中的TUNEL阳性细胞明显减少。SAH后凋亡相关蛋白P53、AIF和细胞色素C上调，但不受阿托伐他汀影响。此外，阿托伐他汀治疗可使SAH后caspase-3和caspase-8在mRNA和蛋白水平的上调均降低。
基于目前的结果，阿托伐他汀在SAH后的神经保护作用可能与其抑制caspase依赖性促凋亡途径有关。
