| Objective To investigate the phosphorylation status of p38αandβin hyperglycemiacerebral reperfusion injury,and their expression and the space-time rules in cells.To explorethe role of p38MAPK in hyperglycemia aggravating cerebral ischemia injury.Methods Type I diabetes hyperglycemia rat model was established Usingstreptozotocin. Through middle cerebral artery occlusion(MCAO)，diabetes hyperglycemiacerebral ischemia reperfusion injury mode in rat1was established. Applying histology，histochemistry，immunofluorescence and western blot，the phosphorylation status of p38αand β (p-p38α,p-p38β)of diabetes hyperglycemia cerebral ischemia reperfusiongroup(hyperglycemia group) and normoglycemia cerebral ischemia reperfusiongroup(normoglycemia group)at30minutus after cerebral ischemia1d,3d,7d,14d and28d afterreperfusion were observed and compared.Results (1)All rats had nerve function defects after focal cerebral ischemia/reperfusioninjury.The brain function scores of hyperglycemia group were obviously higher thanhyperglycemia group (P<0.05).(2)Brain edema, neurons swelling, contraction, and evendeath could be decteted in normoglycemia group at30min after cerebral ischemia，1d afterreperfusion.Neurons and astrocytes dissolution necrosis and became cavity structure inischemia central after3d reperfusion.Brain edema relieved and neurons reduced after7dreperfusion.And parts of the neurons nuclear became light.Glial cells can be detectedaround swelling neurons.Range of infarction area reduced after14d reperfusion and therewas no obvious brain edema.Glial cells increased,gathered in groups and formed glial cells nodules.Compared with normoglycemia group,the number of dead neurons in hyperglycemiagroup was significantly increased,and also the number of astrocytes around dead neurons after30min ischemia and1d,3d reperfusion.Brain edema aggravated, infarct scope and neuronswelling, contraction, and dissolve increased. The number of glial cells increased in ischemiacentral.(3)The results of phosphorylation p38αimmunohistochemistry and Western blotmethods:Sham-operated group and the ischemia group of the left fide brain found only a littleamount of weakly positive p-p38α-labeled cells. Compared with sham-operated group andthe ischemia group of the left fide brain,the ischemia group was significantdifference(P<0.05). In normoglycemia group:p-p38α-labeled cells started to increase at3d,reaching a peak value at14d and reduced at28d.Compared with normoglycemia group,p-p38α-labeled cells in hyperglycemia group between different subgroups had the sameexpression trends. The hyperglycemia group was higher than normoglycemia group at thesame time point(P<0.05).(4)The results of Phosphorylation p38βby immunohistochemistryand Western blot methods:Sham-operated group and the ischemia group of the left fide brainfound only a little amount of weakly positive p-p38β-labeled cells. Compared withsham-operated group and the ischemia group of the left fide brain,the ischemia group wassignificant (P<0.05).There was no significant difference between different subgroups insichemia group. The hyperglycemia group was higher than normoglycemia group at the sametime point(P<0.05).(5)The results of phosphorylation p38αandβby immunofluorescencedouble labeling method:p-p38αpositive cells were co-staind with NeuN, a neuron marker inthe early days of ischemia and reperfusion,and were co-staind with CD68, a microglia markerin the later. P-p38βpositive cells were co-staind with NeuN.Conclusion (1)It is visible in clinical and animal experimental research that，hyperglycemia can increase brain ischemia-reperfusion injury, increase the area of cerebralinfarction and edema, increase ischemia-reperfusion-induced neuronal degeneration andapoptosis, thus exacerbating the neurological symptoms and sign.(2)In rats with focal cerebral ischemia reperfusion model,p38αandβ are all activated in damage.Hyperglycemia mayincrease p38α and β activation degree, thus aggravating cerebral ischemia-reperfusioninjury.(3) P38α and β are available through the aggravating neuronal damage therebyaggravating cerebral ischemia reperfusion injury.(4)P38MAPK signaling pathway can occurthrough different levels of phosphorylation and activated state, and by adjusting its upstreamand downstream factors, involved in mediating hyperglycemia is aggravating cerebralischemia-reperfusion injury. |
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