Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy.
Brain Res. 2011 Feb 4;1372:92-102. doi: 10.1016/j.brainres.2010.11.088. Epub 2010 Dec 4.
NADPH oxidase is a major complex that produces reactive oxygen species (ROSs) during the ischemic period and aggravates brain damage and cell death after ischemic injury. Although many approaches have been tested for preventing production of ROSs by NADPH oxidase in ischemic brain injury, the regulatory mechanisms of NADPH oxidase activity after cerebral ischemia are still unclear. The aim of this study is identifying apocynin as a critical modulator of NADPH oxidase and elucidating its role as a neuroprotectant in an experimental model of brain ischemia in rat. Treatment of apocynin 5min before of reperfusion attenuated cerebral ischemia in rats. Administration of apocynin showed marked reduction in infarct size compared with that of control rats. Medial carotid artery occlusion (MCAo)-induced cerebral ischemia was also associated with an increase in, nitrotyrosine formation, as well as IL-1β expression, IκB degradation and ICAM expression in ischemic regions. These expressions were markedly inhibited by the treatment of apocynin. We also demonstrated that apocynin reduces levels of apoptosis (TUNEL, Bax and Bcl-2 expression) resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. This new understanding of apocynin induced adaptation to ischemic stress and inflammation could suggest novel avenues for clinical intervention during ischemic and inflammatory diseases.
NADPH 氧化酶是一种主要的复合物，在缺血期间产生活性氧物种 (ROS)，并加重缺血性损伤后的脑损伤和细胞死亡。尽管已经测试了许多方法来防止缺血性脑损伤中 NADPH 氧化酶产生 ROS，但 NADPH 氧化酶活性的调节机制仍不清楚。本研究的目的是确定白杨素作为 NADPH 氧化酶的关键调节剂，并阐明其在大鼠脑缺血实验模型中的神经保护作用。在再灌注前 5 分钟给予白杨素治疗可减轻大鼠的脑缺血。与对照组大鼠相比，给予白杨素可显著减少梗死面积。颈内动脉闭塞 (MCAo) 诱导的脑缺血也与缺血区硝基酪氨酸形成以及 IL-1β 表达、IκB 降解和 ICAM 表达增加有关。白杨素治疗明显抑制了这些表达。我们还表明，白杨素降低了细胞凋亡水平 (TUNEL、Bax 和 Bcl-2 表达)，从而减少了缺血再灌注脑损伤中的梗死体积。这种对白杨素诱导的对缺血应激和炎症适应的新认识，可能为缺血性和炎症性疾病的临床干预提供新的途径。
