| Backgrounds:Stroke is a group of syndromes due to the interruption ofcerebral blood flow. It is characterized by a high incidence and high morbidityand high mortality. Advances in intravascular techniques and thrombolyticagents have reduced functional deficits within an optimal time window instroke patients. However, reperfusion itself generates an overproduction ofreactive oxygen species (ROS) or free radicals, leading to reperfusion injury.Ischemic postconditioning is defined in the field of cerebral ischemia researchas a series of brief occlusions and reperfusions applied at the onset ofestablishing reflow, which has proved to be effective against cerebral ischemia.Zhao et al found that postconditioning reduced the infarct size by80%,51%,and17%, respectively, in15,30, or60-min common carotid artery occlusioncombined with permanent distal middle cerebral artery occlusion. Pignataro etal had also shown a very strong protection with postconditioning in anotherfocal ischemic model, in which the middle cerebral artery was occluded for100min. Clinical ischemic stroke in diabetic patients is very common. Diabetesmellitus (DM) is widely recognized as important risk factor for stroke. It is ofgreat significance for ischemic postconditioning in the clinical application toinvestigate whether ischemic postconditioning still has the role of inhibition ofischemia-reperfusion injury in diabetic state.Objective: To investigate whether ischemic postconditioning in thediabetic state still has a protective effect on focal cerebral ischemia and discussthe probable mechanism of ischemic postconditioning in normal blood glucosestate and diabetic state.Methods: We fed the male Sprague-Dawley rats with high fat diet for4 weeks and then injected streptozotocin (STZ) in order to establish diabetic ratmodels. Normal SD rats and diabetic SD rats were treated with ischemicpostconditioning after60minutes of middle cerebral artery occlusion at theonset of reperfusion. Neurologic scores, infarct volumes with TTC staining andhistopathology of cerebral ischemia were assessed at24hours. Oxidative stresswas evaluated by detecting the activity of superoxidase dismutase (SOD),glutathione peroxidase (GSH-pX) and malondialdehyde (MDA) assay.Apoptosis-related molecules such as Bcl-2, Bax and caspase-3were studied byimmunohistochemical staining. Protein kinase B (PKB/Akt) was also tested byWestern blotting and immunohistochemical staining. We compared the effect ofischemic postconditioning in normal rats and diabetic rats.Results: Our results showed that compared with ischemia/reperfusiongroup, ischemic postconditioning significantly reduced the size of ischemicinfarction and improved the neurologic scores at24hours of ischemic/reperfusion injury in normal blood glucose state. Ischemic postconditioningcould also reduce the number of TUNEL positive cells in the ischemicpenumbra in normal rats. But the protective effect of ischemic postconditioningwas not seen in the diabetic state. Postconditioning failed to decrease infarctvolume or improve the neurologic scores in diabetic rats. Postconditioningincreased the activity of SOD and GSH-pX in the brain tissue in the normalstate but not in the diabetic rats when measured at ischemia-reperfusion24hours; Postconditioning decreased the level of MDA in the brain tissue innormal rats but not in the diabetic rats; Postconditioning treatment upregulatedBcl-2and p-Akt protein expression and downregulated Bax and caspase-3activity in normal rats but not in the diabetic rats.Conclusions: Ischemic postconditioning has protective effect for focalischemia-reperfusion injury in normal rats. Chronic hyperglycemia canabrogate the protection of postconditioning at least in part via oxidative stress, cell apoptosis and Akt phosphorylation dysfunction. |
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