Effect of mild hypothermia on the expression of hypoxia-inducible factor-1a and glucose transporter-1 in a rat model of chronic cerebral ischemia-reperfusion

Abstract

Objective To investigate the effect of mild hypothermia on the expression of hypoxia-inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) in a rat model of chronic cerebral ischemia-reperfusion.Methods Thirty-six female SD rats weighing 170-210 g were randomly divided into 3 groups (n = 12 each):sham operation group (group S), normal body temperature group (group NT ) and mild hypothermia group (group MH). Arterio-venous fistula was established by end-to-end anastomosis between the right common carotid artery and right external jugular vein for 6 weeks followed by reperfusion. In group MH, mild hypothermia was induced at the initiation of reperfusion and the rectal temperature was reduced to 31.5-32.5 ℃. In group S and NT, the rectal temperature was maintained at 37-38 ℃. Six rats in each group were sacrificed at 3 and 48 h of reperfusion. The brains were immediately removed for determination of the expression of HIF-1α, GLUT-1, HIF-1α mRNA and GLUT-1 mRNA and microscopic examination. Results Compared with group S, the expression of HIF-1α and HIF-1α mRNA at 3 and 48 h of reperfusion and GLUT-1 mRNA at 3 h of reperfusion was up-regulated, while the expression of GLUT-1 and GLUT-1 mRNA at 48 h of reperfusion was down-regulated in group NT (P ＜ 0.05).Compared with group NT, the expression of HIF-1α and HIF-1α mRNA at 48 h of reperfusion and HIF-1α mRNA and GLUT-1 mRNA at 3 h of reperfusion was down-regulated, while the expression of GLUT-1 and GLUT-1 mRNA at 48 h of reperfusion was up-regulated in group MH (P ＜ 0.05).Microscopic examination showed that the injury to the ultrastructure of blood-brain barrier was significantly attenuated in group MH compared with group NT. Conclusion Mild hypothermia can attenuate chronic ischemia-reperfusion injury by down-regulating the expression of HIF-1α and up-regulating the expression of GLUT-1. Key words: Hypothermia, induced; Reperfusion injury; Brain; Hypoxia-inducible factor 1, alpha subunit; Glucose transporter type 1