5-Lipoxygenase Inhibitor Zileuton Inhibits Neuronal Apoptosis Following Focal Cerebral Ischemia

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• 作者：Song-sheng Shi (1)
  Wei-zhong Yang (1)
  Xian-kun Tu (1)
  Chun-hua Wang (1)
  Chen-mei Chen (1)
  Yan Chen (1)
  
• 关键词：apoptosis ; cerebral ischemia ; cleaved caspase ; 3 ; 5 ; lipoxygenase
• 刊名：Inflammation
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：36
• 期：6
• 页码：1209-1217
• 全文大小：
• 作者单位：Song-sheng Shi (1)
  Wei-zhong Yang (1)
  Xian-kun Tu (1)
  Chun-hua Wang (1)
  Chen-mei Chen (1)
  Yan Chen (1)
  
  1. Department of Neurosurgery, Fujian Medical University Union Hospital, Fujian Neurosurgical Institute, 29# Xinquan Road, Fuzhou, Fujian, 350001, China
  
• ISSN：1573-2576

文摘

Previous studies from our laboratory demonstrated that zileuton, a selective 5-lipoxygenase (5-LOX) inhibitor, attenuates ischemic brain damage in rats of focal cerebral ischemia. Enormous evidences showed that inflammatory reaction and neuronal apoptosis are the two important pathophysiological events in ischemia-induced brain damage. Our previous studies demonstrate that zileuton attenuates ischemic brain damage via inhibiting inflammatory reaction. The present study was performed to explore whether 5-LOX inhibitor zileuton attenuates neuronal apoptosis following focal cerebral ischemia and further investigate the potent mechanisms underlying its neuroprotection. Adult male Spragueawley rats underwent permanent middle cerebral artery occlusion (MCAO) for 72h, then received intragastric gavage with zileuton or vehicle as a bolus after the onset of MCAO. Neurological deficit scores, cerebral infarct volume, and neuronal damage were measured 72h after MCAO. TUNEL staining was performed to measure the extent of neuronal apoptosis. Reverse transcription-polymerase chain reaction was performed to determine the expression of caspase-1 mRNA. Western blot was performed to determine the expression of procaspase-3 and cleaved caspase-3 in rat brain. Neurological deficit scores, infarct volume, and neuronal damage were significantly attenuated by administration of zileuton. MCAO caused the elevation of neuronal apoptosis, which was significantly inhibited by the administration of zileuton. MCAO caused the over-expression of caspase-1 and cleaved caspase-3, both of which were significantly inhibited by the administration of zileuton. Expression of procaspase-3 was reduced after MCAO, which was significantly up-regulated by administration of zileuton. Our studies suggested that 5-LOX inhibitor zileuton reduces MCAO-induced brain damage and neuronal apoptosis, which might be associated with the inhibition of caspase-1 and the regulation of caspase-3.