Effect of pre-ischemia on hypoxia-inducible factor expression in the brain tissue of rats with cerebral ischemia/reperfusion injury

BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) can lead to the adaptative reaction of body for hypoxia and ischemia. HIF-1 plays an important role in the response of ischemia-hypoxia. At present, there has been no overall report on the significance for the expression of HIF-1 following experimental cerebral ischemia. OBJECTIVE: To observe the expression of HIF-1 after middle cerebral artery occlusion (MCAO) by immunohistochemical method. DESIGN: Completely randomly grouped controlled animal experiment. SETTING: Second Hospital, Xi'an Jiaotong University. MATERIALS: Thirty-six Sprague-Dawley healthy male rats, with body mass of 250–330 g, were used in this study. Thirty-six rats were randomized into 3 groups: pre-ischemia group, sham-operation group and control group, with 12 rats in each. METHODS: This study was carried out in the clinical laboratory, People's Hospital of Ningjin County of Shandong Province from March 2006 to January 2007. Rats in the pre-ischemia group were created into pre-ischemia models by two embolisms twice. Three days after ischemic preconditioning, middle cerebral artery (MCA) was occluded for 2 hours with the same method. After being perfused for 22 hours, the rats were euthanized. In the sham-operation group, rats were not given the treatment of pre-ischemia. In the first operation, only common carotid artery (CCA) and its crotch were exposed in the first operation, and MCA was not blocked by inserting embolism. At postoperative 3 days, rats were euthanized after being subjected to MCAO for 2 hours and reperfusion 22 hours by the same procedure as that in the pre-ischemia group. As for each rat in the control group, only CCA and its crotch were exposed, and no any other treatment was carried out on them. MAIN OUTCOME MEASURES: Brain tissue of each rat was performed immunohistochemical staining at reperfusion 22 hours after pre-ischemia, HIF-1 expression and brain infarct volume were detected. RESULTS: Thirty-six Sprague-Dawley rats were involved in the experiment. During the experiment, 8 rats dropped out, and another 8 rats were supplemented. The infarct volume of rats in the pre-ischemia group was significantly smaller than that in the sham-operation group （t =3.22, P < 0.01）. HIF-1 expression was not found in the control group, but many HIF-1 positive cells were found in the other two groups. Absorbance in the pre-ischemia group was significantly higher than that in the sham-operation group (t =4.31, P < 0.01). CONCLUSION: Slight ischemia caused preconditioning can increase HIF-1 content, and it is one of protective mechanisms for nerve cells.

Effect of pre-ischemia on hypoxia-inducible factor expression in the brain tissue of rats with cerebral ischemia/reperfusion injury