The Effect Of Mitochondrial Uncoupling Protein 2 On Hyperglycemia Exaggerated Cerebral Ischemic Injury And It's Relationship With Mitochondria Fission And Fusion

Objective To investigate effects and its possible mechanism of mitochondrial uncoupling protein 2 on hyperglycemia exaggerated cerebral ischemic injury and it's relationship with mitochondria fission and fusion.Methods KO-UCP2 and WT mice were randomly divided into two groups:hyperglycemia group(measurement of fasting glucose exceeded 14mmol/L after STZ-induced for 72h)and non-hyperglycemia group(without STZ-induced).Then all mice respectively were divided into sham operation group(Sham)and cerebral ischemia model group(MCAO).Cerebral artery occlusion surgery was preparation for all KO-UCP2 mice and WT mice in cerebral ischemia model group.We treated all mice in according to the reperfusion of 6,24,72 hours.We evaluated models with using neurological deficits,observed infarct size of mice' brain with TTC staining and observed morphological changes of nerve cells with HE staining,Nissl staining;Apoptosis was determined via flow cytometry;The expression of Fis1,Drp1,Opa1 and Mfn2 was detected by the immunohistochemistry.The expression of Fis1,Drp1,Opa1 and Mfn2 mRNA was detected by the RT-PCR.Results 1.KO-UCP2 further increaseed the score of neural function,increased the infarct volume,enhanced brain tissue morphological damage,with hyperglycemia-exaggerated cerebral ischemic injury.2.KO-UCP2 promoted apoptosis with hyperglycemia-exaggerated cerebral ischemic injury.3.KO-UCP2 further increased the expression of the mitochondrial fission related factor Fis1 and Drp1,decreased the expression of the mitochondrial fussion related factor Opa1 and Mfn2 with hyperglycemia-exaggeratedcerebral ischemic injury.5.KO-UCP2 promoted the expression of Fis1 mRNA and Drp1 mRNA,decreased the expression of Opa1 mRNA and Mfn2 mRNA.Conclusions1.KO-UCP2 can enhance hyperglycemia-exaggerated cerebral ischemic injury.2.KO-UCP2 increases ischemic brain damage through induced apoptosis.3.KO-UCP2 impairs the balance of mitochondrial fission and fusion.