Rosuvastatin preconditioning provides neuroprotection against spinal cord ischemia in rats through modulating nitric oxide synthase expressions
Rosuvastatin preconditioning provides neuroprotection against spinal cord ischemia in rats through modulating nitric oxide synthase expressions
复制标题
瑞舒伐他汀预处理通过调节一氧化氮合酶表达对大鼠脊髓缺血提供神经保护
DOI：
10.1016/j.brainres.2010.05.068
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发表时间：
2010-07-30
期刊：
影响因子：
2.9
通讯作者：
Shi, Zhibing
中科院分区：
文献类型：
--
作者：
Die, Jun;Wang, Kunzheng;Shi, Zhibing
本研究旨在探讨瑞舒伐他汀对大鼠脊髓缺血的保护作用及其对一氧化氮合酶（NOS）表达的影响。通过阻塞降胸主动脉在雄性Sprague-Dawley大鼠中诱导脊髓缺血。实验组（n=30/组）如下：假手术、对照（仅接受生理盐水）、瑞舒伐他汀（阻塞前5 mg/kg/天持续10天）和瑞舒伐他汀-甲羟戊酸（阻塞前5 mg/kg/天瑞舒伐他汀和5 mg/kg/天甲羟戊酸持续10天）。分别于再灌注后6、12、24、48、72 h检测神经功能。再灌注72 h后，取脊髓行TTC染色、TUNEL染色、一氧化氮（NO）测定。神经元NOS（iNOS、eNOS和nNOS）如此诱导的脊髓缺血以神经功能障碍、脊髓梗塞，结果表明，瑞舒伐他汀显著减少了治疗大鼠的运动障碍和梗死体积，并减少了神经细胞凋亡。脊髓组织中NO水平此外，瑞舒伐他汀抑制NOS mRNA和蛋白表达，增加eNOS mRNA和蛋白表达，然而，瑞舒伐他汀对nNOSmRNA和蛋白表达无影响甲羟戊酸的给药完全逆转了瑞舒伐他汀引起的变化这些结果表明瑞舒伐他汀可以通过调节NOS表达来保护大鼠脊髓免受缺血损伤（C）2010爱思唯尔B V版权所有
The study was aimed to investigate the protective effects of rosuvastatin on spinal cord ischemia in rats and to determine the effects of this agent on the expressions of nitric oxide synthase (NOS). Spinal cord ischemia was induced in male Sprague-Dawley rats by occluding the descending thoracic aorta Experimental groups (n=30 per group) were as follows sham operation, control (receiving only normal saline), rosuvastatin (5 mg/kg/day for 10 days before occlusion), and rosuvastatin-mevalonate (5 mg/kg/day rosuvastatin and 5 mg/kg/day mevalonate for 10 days before occlusion). Neurological function was assessed at 6, 12, 24, 48, and 72 h after reperfusion After 72 h reperfusion, spinal cords were harvested for 2,3,5,-triphenyltetrazolium chloride (TTC) staining, TUNEL staining, and nitric oxide (NO) assay Immunohistochemistry, reverse transcription polymerase chain reaction and western blot were performed to determine the expressions of inducible, endothelial, and neuronal NOS (iNOS, eNOS, and nNOS) in rats with spinal cord ischemia Spinal cord ischemia thus induced was marked by neurological dysfunction, spinal infarction, and neural cell apoptosis in animals The results show that rosuvastatin significantly reduced the motor disturbance and the volume of infarctions and attenuated apoptotic neural cells death in the treated rats Treatment with rosuvastatin remarkably decreased the NO level in spinal cord tissue In addition, rosuvastatin inhibited NOS mRNA and protein expression and increased eNOS mRNA and protein expression However, rosuvastatin had no influence on nNOS mRNA and protein expression Administrations of mevalonate completely reversed the changes caused by rosuvastatin These results indicate that rosuvastatin can protect rat spinal cord against ischemia injury by modulation of NOS expressions (C) 2010 Elsevier B V All rights reserved