Effect of chelating zinc on expression of hypoxia inducible factor-1α in the penumbra of rats following focal cerebral ischemia/reperfusion

doi:10.3969/j.issn.1006-7795.2016.05.014

Abstract

Abstract: Objective To investigate the dynamic changes of hypoxia inducible factor-1α (HIF-1α) during reperfusion in a rat middle cerebral artery occlusion (MCAO)/reperfusion model and the changes of HIF-1α expression by removing zinc with zinc chelatorN,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine, TPEN], and to explore the probable mechanism by which zinc involved in cerebral ischemia/reperfusion injury. Methods Forty-five male Sprague Dawley rats were divided into three groups randomly:Sham group, MCAO group, and MCAO+TPEN grouprats received TPEN (15mg/kg, i.p.) once 30 min before MCAO]. There were 15 rats in each group. MCAO operation was performed by using suture method. The rats underwent right MCAO for 90 min. The rectal temperature and mean arterial blood pressure were monitored to keep in normal range during the operation. At 3, 12 or 24 h after reperfusion, brains were removed. The expression and location of HIF-1α were detected by immunohistochemistry and immunofluorescent staining. Results 1) No HIF-1α positive cell was observed in the brain of Sham group rats. The number of HIF-1α positive cells in the penumbra of MCAO group showed time-dependent increasing tendency within 24 hours after reperfusion (P<0.01). 2) At 3, 12 and 24 h after reperfusion, the numbers of HIF-1α positive cells in the penumbra of MCAO+TPEN group rats decreased significantly compared with those of MCAO group rats (P<0.01). 3) HIF-1α-positive immunoreactive cells were colocalized with the general neuronal marker, NeuN, in MCAO rats. Conclusion The level of HIF-1α in neurons increased along with the extension of reperfusion time in focal cerebral ischemia/reperfusion rats. The expression of HIF-1α was decreased by removing intracellular zinc in MCAO rats, suggesting that zinc may be involved in the ischemia/reperfusion injury by promoting the expression of HIF-1α.

Key words: zinc, hypoxia inducible factor-1α (HIF-1α), brain ischemia, reperfusion, rats

CLC Number:

R743

Fang Yalan, Li Sen, Zhao Yongmei, Yan Feng, Yin Jie, Luo Yumin, Liu Kejian. Effect of chelating zinc on expression of hypoxia inducible factor-1α in the penumbra of rats following focal cerebral ischemia/reperfusion[J]. Journal of Capital Medical University, 2016, 37(5): 626-630.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2016.05.014

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2016/V37/I5/626

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