Diabetes Aggravate The Ischemic Damage After The Ischemia/Reperfusion Through Oxidative Damage

Objective:Hyperglycemia contributes to the aggravated ischemic damage afterthe ischemia/reperfusion(I/R) injury,but the oxidative damage of neurons andastrotytes are not clear.To observe the role and mechanism of oxidative damageof neurons and astrotytes in the brain ischemic rats with hyperglycemia.Methods:The male SD rats were randomly assigned into normoglycemic focalcerebral I/R group (normoglycemic group), diabetic hyperglycemic I/R group(diabetes group) and the sham groups.The rats were injected intraperitoneallywith streptozotocin (STZ,55mg/kg) to induce the diabetic hyperglycemia. Thefocal cerebral I/R was induced by middle cerebral artery occlusion (MCAO) inrats.Cerebral ischemia30-min and reperfusion at1-,7-, and14-d was inducedin3days after STZ-induced diabetic hyperglycemia.The damage ofneurons,astrocytes and the relationship of the both two with8-OHdG werecomparably ovserved using histology and immunohistochemistry,stain of NeuN and8-OHdG,stain of GFAP and8-OHdG.Results:Histological examination showed that cerebral edema was observedin normoglycemic group at1-d after reperfusion,while worse cerebral edema,evenneuronal pyknosis were appeared in diabetic group.More serious cerebral edemawas showed in normoglycemic group at3-d after reperfusion,even more neuronalpyknosis were observed.The majority of cells were necrosis with frothhistiocytes.The diabetic group was also more serious.The cerebral edema andneuronal pyknosis was decreased and disappeared in normoglycemic group at7-d after reperfusion.However, there was few neuronal pyknosis and edema in diabeticgroup.At14-d after reperfusion, The gliosis, but no brain edema and neuronalpyknosis, was observed in the normoglycemic group. The mild edema was stillproved diabetic group.Immunohistochemistry showed that the number of8-OHdGpositive cells was significantly increased at3-d after reperfusion in bothnormoglycemic and diabetic rats compared with sham group.More8-OHdG positivecells were observed in diabetic rats compared with normoglycemic group（P<0.05）.Although the number of8-OHdG positive cells and neurons wassignificantly decreased at7-, and14-d after reperfusion,in both normoglycemicand diabetic rats compared with1-d reperfusion,the positive cells wassignificantly more than that sham group（P<0.05).Stain of NeuN and8-OHdG,GFAPand8-OHdG showed that the8-OHdG positive neurons was up to the peak at3-dafter reperfusion,and more8-OHdG positive neurons were observed in diabeticrats compared with normoglycemic group（P<0.05）.The8-OHdG positive neuronswere decreased at7-and14-d after reperfusion.The8-OHdG positive astrocyteswas begin to increase at3-d after reperfusion,up to the peak at7-d afterreperfusion.More8-OHdG positive astrocytes were observed in diabetic ratscompared with normoglycemic group（P<0.05）.The number of8-OHdG positiveastrocytes was significantly decreased at14-d after reperfusion,but thepositive cells was significantly more than that sham group（P<0.05).Conclusion:(1)Hyperglycemia aggravates the I/R injury,worse cerebral edemawas observed in infarcted area and around the infarction.In diabetic group,theinfarcted area was larger,more degeneration and apoptosis in neurons wereappeared than normoglycemic group.(2)I/R may cause oxidative damage,and theworse damage was observed at1-d after reperfusion.At3-d after reperfusion,theoxidative damage was up to the peak.However,the level of oxidative injury was decreased at7-d after reperfusion.In diabetic group,worse oxidative damage wasobserved at1-d and3-d after reperfusion,and the extent of decrease was largerthan normoglycemic group at7-d after reperfusion.(3)The oxidative injury wassignificantly increased at1-d and3-d after cerebral ischemia30min.Theoxidative damage mainly occurs in neurons.Hyperglycemia may significantlyaggravate the oxidative injury of neurons,and the oxidative injury of astrocyteswas mild.