Ferulic acid modulates nitric oxide synthase expression in focal cerebral ischemia.
Ferulic acid modulates nitric oxide synthase expression in focal cerebral ischemia.
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DOI：
10.5625/lar.2012.28.4.273
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发表时间：
2012-12
影响因子：
2.9
通讯作者：
Koh PO
中科院分区：
文献类型：
--
作者：
Koh PO
一氧化氮（NO）由三种不同的NO合酶（NOS）亚型产生，即内皮型NOS（eNOS）、诱导型NOS（iNOS）和神经型NOS（nNOS）。已知eNOS产生发挥保护作用的NO，而iNOS产生具有神经毒性作用的NO。阿魏酸保护神经细胞免受脑缺血和谷氨酸诱导的兴奋性毒性。本研究证实了阿魏酸的神经保护作用，并研究了三种NOS亚型在有或没有阿魏酸的局灶性脑缺血中的水平。将大鼠立即用阿魏酸（100 mg/kg，i. v.）大脑中动脉闭塞（MCAO）后。在闭塞开始后24小时收集脑组织。采用Western blot技术分析阿魏酸对脑缺血后上述3种亚型的表达影响。阿魏酸治疗显著减少大脑皮层中TUNEL阳性细胞的数量，对抗MCAO损伤。在MCAO手术动物中，eNOS水平降低，而阿魏酸治疗减弱了MCAO诱导的eNOS降低。然而，iNOS和nNOS的表达水平增加，在MCAO，和阿魏酸防止这些亚型的损伤诱导的增加。因此，这些发现表明，阿魏酸对三种亚型的上调和下调与神经保护机制有关。
Nitric oxide (NO) is generated by three different NO synthase (NOS) isoforms, endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS). It is known that eNOS produces NO, which exerts a protective effect, while iNOS produces NO with neurotoxic effects. Ferulic acid preserves neuronal cells against from cerebral ischemia and glutamate-induced excitotoxicity. This study confirmed the neuroprotective effect of ferulic acid and investigated the levels of three NOS isoforms in focal cerebral ischemia with or without ferulic acid. Rats were immediately treated with ferulic acid (100 mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brains tissues were collected at 24 h after the onset of occlusion. The expressions of these three isoforms in cerebral ischemia with ferulic acid were analyzed using Western blot technique. Ferulic acid treatment significantly decreases the number of TUNEL-positive cells in the cerebral cortex against MCAO injury. The levels of eNOS decreased in MCAO-operated animals, while ferulic acid treatment attenuated the MCAO-induced decrease of eNOS. However, iNOS and nNOS expression levels increased during MCAO, and ferulic acid prevented injury-induced increase of these isoforms. Thus, these findings suggest that the up- and down modulation of three isoforms by ferulic acid is associated with a neuroprotective mechanism.