Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Brain Res. 2010 Apr 14;1325:164-73. doi: 10.1016/j.brainres.2010.02.036. Epub 2010 Feb 16.
It has been proved that chronic administration and pre-treatment with atorvastatin could protect brain tissue against ischemic injury. However, little is known regarding the effect of atorvastatin in the acute phase of ischemic stroke. This study investigated the potential neuroprotective effects of atorvastatin and underlying mechanisms in vivo.
Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). Experiment 1 was used to evaluate time course expressions of 12/15-LOX, mitogen-activated protein kinase (MAPK), phosphorylated-p38MAPK (phospho-p38MAPK) and cytosolic phospholipase A2 (cPLA2) after cerebral ischemia, seven time points were included. Experiment 2 was used to detect atorvastatin's neuroprotection in the acute phase of ischemic stroke; atorvastatin was administered immediately after MCAO. Neurological deficit, brain water content and infarct size were measured at 24h after stoke. Immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to analyze the expression of 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2. Experiment 3 was used to detect atorvastatin's influence on blood-brain barrier (BBB).
12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2 were up-regulated after cerebral ischemia. Compared with MCAO group, atorvastatin dramatically reduced brain water content and infarct sizes, and the over-expressions of 12/15-LOX, p38MAPK, phospho-p38MAPK and cPLA2 were significantly decreased in high dose group (20mg/kg, P<0.05). Meanwhile, extra-vascular IgG was not only reduced, but BBB permeability was also ameliorated.
Atorvastatin protected brain from damage caused by MCAO at the early stage; this effect may be through down-regulation of 12/15-LOX, p38MAPK and cPLA2 expressions, and ameliorating BBB permeability.
已有研究证实，阿托伐他汀的慢性给药和预处理可保护脑组织免受缺血性损伤。然而，关于阿托伐他汀在缺血性脑卒中急性期的作用知之甚少。本研究旨在体内研究阿托伐他汀的潜在神经保护作用及其机制。
雄性 Sprague-Dawley 大鼠接受永久性大脑中动脉闭塞（MCAO）。实验 1 用于评估缺血后 12/15-LOX、丝裂原活化蛋白激酶（MAPK）、磷酸化 p38MAPK（phospho-p38MAPK）和胞质型磷脂酶 A2（cPLA2）的时间表达，共包括 7 个时间点。实验 2 用于检测阿托伐他汀在缺血性脑卒中急性期的神经保护作用；MCAO 后立即给予阿托伐他汀。卒后 24h 测量神经功能缺损、脑水含量和梗死体积。免疫组织化学、逆转录-聚合酶链反应（RT-PCR）和 Western blot 用于分析 12/15-LOX、p38MAPK、phospho-p38MAPK 和 cPLA2 的表达。实验 3 用于检测阿托伐他汀对血脑屏障（BBB）的影响。
缺血后 12/15-LOX、p38MAPK、phospho-p38MAPK 和 cPLA2 表达上调。与 MCAO 组相比，阿托伐他汀显著降低脑水含量和梗死体积，高剂量组（20mg/kg）12/15-LOX、p38MAPK、phospho-p38MAPK 和 cPLA2 的过度表达明显降低（P<0.05）。同时，血管外 IgG 减少，BBB 通透性改善。
阿托伐他汀在 MCAO 早期阶段保护大脑免受损伤；这种作用可能是通过下调 12/15-LOX、p38MAPK 和 cPLA2 的表达，改善 BBB 通透性实现的。
