Changes of hypoxia-inducible factor-1 signaling and the effect of cilostazol in chronic cerebral ischemia*
Han Chen
Aixuan Wei
Jinting He
Ming Yu
Jing Mang
Zhongxin Xu
摘要：Hypoxia-inducible factor-1 and its specific target gene heme oxygenase-1, are involved in acute cerebral ischemia. However, very few studies have examined in detail the changes in the hypox-ia-inducible factor-1/heme oxygenase-1 signaling pathway in chronic cerebral ischemia. In this study, a rat model of chronic cerebral ischemia was established by permanent bilateral common carotid artery occlusion, and these rats were treated with intragastric cilostazol (30 mg/kg) for 9 weeks. Morris water maze results showed that cognitive impairment gradual y worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative PCR and western blot analysis showed that hypoxia-inducible factor-1α and heme oxygenase-1 expression levels in-creased after chronic cerebral ischemia, with hypoxia-inducible factor-1α expression peaking at 3 weeks and heme oxygenase-1 expression peaking at 6 weeks. These results suggest that the elevated levels of hypoxia-inducible factor-1α may upregulate heme oxygenase-1 expression fol-lowing chronic cerebral ischemia and that the hypoxia-inducible factor-1/heme oxygenase-1 sig-naling pathway is involved in the development of cognitive impairment induced by chronic cerebral ischemia. Cilostazol treatment al eviated the cognitive impairment in rats with chronic cerebral is-chemia, decreased hypoxia-inducible factor-1α and heme oxygenase-1 expression levels, and re-duced apoptosis in the frontal cortex. These findings demonstrate that cilostazol can protect against cognitive impairment induced by chronic cerebral ischemic injury through an anti-apoptotic mecha-nism.
机标关键词：cerebral ischemiawestern blot analysiscommon carotid arterysignaling pathwaytarget genewater mazerat model
资助基金：The project was supported by the Natural Science Fundation of Jilin Province in China, (No.200705272)
论文发表日期：2013-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 1803-1813 )
英文信息