Induction of inducible nitric oxide synthase by isoflurane post-conditioning via hypoxia inducible factor-1伪 during tolerance against ischemic neuronal injury

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• 作者：Qi Fang Li ; Hui Xu ; Yu Sun ; Rong Hu ; Hong Jiang ; ^{jiuyuanpaper@yahoo.cn}
• 关键词：Hypoxia inducible factor-1伪 ; Isoflurane ; Inducible nitric oxide synthase ; Ischemia
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：27 April, 2012
• 卷：1451
• 期：Complete
• 页码：1-9
• 文件大小：905 K

摘要

Recent studies have shown that isoflurane protects against ischemic injury via inducible nitric oxide synthase (iNOS). Hypoxia inducible factor (HIF)-1伪 is a transcriptional factor that activates after cerebral ischemia. However, whether iNOS gene containing the sequence of the hypoxia response element (HRE) is a HIF-1伪 target during tolerance against ischemic neuronal injury induced by isoflurane post-conditioning remains unknown. In this study, we report that HIF-1伪 and iNOS gene expression were augmented after cerebral ischemia in rats. Furthermore, isoflurane post-conditioning resulted in greater accumulation of HIF-1伪 and iNOS gene expression, following by HIF-1伪 transcriptional activity enhancement and co-localization of HIF-1伪 and iNOS. Accordingly, in the primary cortical neuron cultures, silencing of HIF-1伪 attenuated the accumulation of iNOS and the protective effects of isoflurane post-conditioning. Our results suggest the involvement of HIF-1伪 in the regulation of iNOS during tolerance against cerebral ischemia induced by isoflurane post-conditioning, which provide a mechanistic basis of novel therapeutic strategies for ischemic stroke.