中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (19): 1803-1813.doi: 10.3969/j.issn.1673-5374.2013.19.008
慢性脑缺血后缺氧诱导因子1α信号通路变化及西洛他唑的作用
Changes of hypoxia-inducible factor-1 signaling and the effect of cilostazol in chronic cerebral ischemia
Han Chen1, 2, Aixuan Wei1, 3, Jinting He1, Ming Yu4, Jing Mang1, Zhongxin Xu1
- 1 Department of Neurology, China-Japan Friendship Hospital, Jilin University, Changchun 130012, Jilin Province, China
2 Department of Neurology, Chang Chun Central Hospital, Changchun 130051, Jilin Province, China
3 Department of Neurology, Jilin City Central Hospital, Jilin 132011, Jilin Province, China
4 Department of Neurology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
摘要：
以往研究结果表明，缺氧诱导因子1和它的特定靶基因血红素加氧酶1可能参与了急性脑缺血。但缺氧诱导因子1/血红素加氧酶1信号通路在慢性脑缺血的变化尚不明确。实验建立永久性双侧颈总动脉闭塞的慢性脑缺血大鼠模型，给予9周30mg/kg西洛他唑灌胃治疗。结果显示，慢性脑缺血大鼠的认知障碍随缺血时间延长而逐渐加重。而以免疫组化和实时定量PCR和Western blot检测到，缺氧诱导因子1和血红素加氧酶1表达水平在慢性脑缺血后提高，缺氧诱导因子1的表达高峰出现在缺血后3周，而血红素加氧酶1表达高峰延迟，出现在缺血后6周，提示血红素加氧酶1在慢性脑缺血条件下被缺氧诱导因子1激活而上调，缺氧诱导因子1/血红素加氧酶1信号通路参与了慢性脑缺血致认知损伤的病理过程。而以西洛他唑干预后，慢性脑缺血大鼠的认知损伤得到改善，缺氧诱导因子1和血红素加氧酶1表达水平下调，额叶皮质中凋亡细胞数量减少，说明西洛他唑通过抗细胞凋亡下调缺氧诱导因子1/血红素加氧酶1信号通路，改善了大鼠的血管性认知功能障碍。