Changes of rat penumbral glucose transporter-3 expression following cerebral ischemia-reperfusion injury / 中国组织工程研究

ABSTRACT

BACKGROUND: Recent researches indicate that ischemia and hypoxia can lead to abnormal brain metabolism and even energy failure, which is an important reason for brain damage and necrosis and identifies energy metabolism disorder as the key event in brain ischemia-reperfusion (IR)injury. Glucose transporter-3 plays the vital role in brain energy metabolism.OBJECTIVE: To observe the changes of cerebral infarct volume and glucose transporter-3 mRNA and protein expressions in cerebral cortical penumbra at different stages of focal cerebral ischemia and reperfusion in rats.DESIGN: Randomized controlled experiment.SETTING: Department of Neurosurgery, Second Hospital Affiliated to Sun Yat-sen University.MATERIALS This experiment was conducted in the Animal Laboratory of Medical Research Center, Second Hospital Affiliated to Sun Yat-sen University between August and October 2002.Totally 56 SD rats were randomized into 3 groups which were subjected to ① ischemia for 1 hour followed by reperfusion (n=28), ② ischemia for 3 hours followed by reperfusion (n=24), and ③ sham operation (n=4). The rats in the first group were subdivided into 7 subgroups for examination at 1, 3, 6, 12, 24, and 72hours and 1 week after ischemia, with 7 rats in each subgroup; the rats in the second ischemia group were also subdivided in similar manner but without a 1 hour postischemic subgroup. The rats in the sham operation group only received the operation but without arterial occlusion.METHODS: Focal cerebral ischemia-reperfusion (IR) injury model was induced in the rats in the two ischemic groups by means of insertion of suture for arterial occlusion, and the ratio of central ischemic area to cerebral infarct volume in the ischemic penumbra was examined at the specified time points. Reverse transcription-PCR (RT-PCR) was used to detect the expression of glucose transporter-3 mRNA in the cerebral cortex in ischemic penumbra region, and semi-quantitative immunohistochemistry (IHC) employed to detect the level of glucose transporter-3 protein.MAIN OUTCOME MEASURES: Cerebral infarct volume after IR injury, changes of transporter-3 mRNA and protein expressions after IR injury.RESULTS: Totally 56 rats were used in this experiment and all entered result analysis. The post-IR cerebral infarct volume was obviously smaller in 1-hour ischemia group than in 3-hour ischemia group. Glucose transporter-3 mRNA expression began to increase 3 hours after ischemia in 1-hour ischemia group, reaching the peak level at 24 hours and still mainrained higher level than that of the sham operation 1 week; in 3-hour ischemia group, the mRNA expression was slightly decreased at 3 hours but began to increase afterwards till reaching the peak level at 24 hours, followed then by recovery of normal level at 1 week. The changes in glucose transporter-3 protein and mRNA expressions followed almost the same pattern.CONCLUSION: Glucose transporter-3 expression is up-regulated in the ischemic penumbra region, possibly as a protective response to cerebral IR injury.