The Influence Of Dexmedetomidine Pretreatment On Global Cerebral Ischemic-reperfusion Injury In Rats

Cerebrovascular disease is a serious public health problem, It is alsoone of the major diseases which causes death and disability in theworld.Ischemic cerebrovascular disease accounts for about70%to80%among all the Cerebrovascular disease.Cerebral ischemia can cause braincell damage and severe neurological dysfunction, when blood flowreperfusion, it also can lead to cerebral ischemia-reperfusion injury.Thiswill make a series of pathophysiological and biochemical changing, andlead to learning and memory impairment, seriously affect the patient’squality of life, even life-threatening.Therefore, to prevent cerebralischemia-reperfusion injury, and find effective treatments and measures,has always been the focus of attention of the life sciences.Dexmedetomidine is a new, efficient, and highly selective alpha2adrenergic agonists,it has some characteristics such as sedative, anxiolytic,analgesic, inhibition of the sympathetic nerve, significantly reduce theamount of anesthetic and stable hemodynamic during anesthesia.Andwith less respiratory depression.In recent years, studies have shown thatDexmedetomidine can reduce brain tissue norepinephrine and excitatoryneurotransmitter release,involved in the regulation of apoptosis,so it isbenefit for neuro-protective in Ischemic brain injury.whetherdexmedetomidine pretreatment also have effect,have not known yet.Objective：By using a modified four-vessel occlusion prepared ratmodel of cerebral ischemia,to observe the effects of different doses ofdexmedetomidine given pretreatment on cerebral ischemia-reperfusioninjury in rats.Through the global cerebral ischemia in the hippocampalCA1region neuropathological testing, detection of brain water content,hippocampus glutamate （glutamic acid, GLU） and r-aminobutyric acid （r-aminobutyric acid, GABA） detection,to reflect whetherdexmedetomidine has cerebral protection by given pretreatment oncerebral ischemia-reperfusion injury in rats.Methods：Male SD rats, aged3-3.5months, weight280-350g, wereused in this study. Global cerebral ischemic-reperfusion was induced byfour-vessel occlusion,with the Ischemic time15mins. Forty rats ofsuccessful model were randomly divided into4groups（n=10each）: shamoperation group（group S）; ischemic-reperfusion control group（group C）;low and medium doses of dexmedetomidine pretreatment groups（groupD₁-2）. In group D₁-2, before ischemia2h, dexmedetomidine0.05and0.5μg·kg^-1·min^-1were infused continuously for2h respectively, whilenormal saline2ml/h were given instead of dexmedetomidine in group Sand C. The changes in the hippocampal CA1pathology and cellultrastructure were observed30min after reperfusion. The brain watercontent was detected by wet and dry weight method. High performanceliquid chromatography-mass spectrometry to detect changes in thehippocampal glutamate acid and r-aminobutyric acid content.Result:1The weight of the rats and the months of age in each group did notappeared significant difference （P>0.05）.2DEX pretreatment on global cerebral ischemia and reperfusionneuropathological observation.S group hippocampal CA1pyramidal cell layer neurons have three tofour layers, arranged in neat tight cell boundaries clear, nuclei were roundor oval, lightly stained, the total cell2/3,1²nucleolus, round, deeplystained. In group C, hippocampal CA1pyramidal cells arranged scattered.Pyramidal nucleus concentrated, deeply stained, edema. In the D₁-2groupcompared with C group reduced. Most pyramidal cells survival. Thenumber of pyknotic neurons and neuronal loss significantly reduced.3DEX pretreatment on cerebral ischemia-reperfusion injury of brainwater content. Compared with the group S, the brain water content was increasedsignificantly in group C,D₁and D₂（P<0.05）; Compared with the groupC, the data did not appeared statistical difference between group D₁andgroup D₂（P>0.05）.4DEX pretreatment on global cerebral ischemia and reperfusion in eachgroup hippocampal CA1neuron ultrastructure.SEM results show that the heaviest damage in group C, C groupshowed obvious edema peripheral nerve cells with cytoplasmicedema.Mitochondrial electron density increased, swelling, cristae,decrease, or even disappear, Golgi vesicles expansion; markedly swollenastrocytes.Capillary endothelial cell swelling, perivascular edema.Pathological changes of the D₁-2compared with C group reduced, but didnot show a significant difference between group D₁and group D₂.5DEX pretreatment on cerebral ischemia-reperfusion injury in eachgroup of glutamate and r-aminobutyric acid.The test results of glutamate show that30mins after global cerebralischemia reperfusion, the four groups was no significant difference in thelevels of glutamate acid. Compared with the S group, the content ofr-aminobutyric acid was decreased significantly in grouo C （P <0.05）. Ingroup D₁and group D₂,the content of r-aminobutyric acid decreased withno significant difference. Compared with the C group, the content ofr-aminobutyric acid was increased significantly in group D₁and D₂（P<0.05）, but the data did not appeared statistical difference between groupD₁and group D₂.Conclusions：In Global cerebral ischemia-reperfusion injury with rats,the low dose group and middle dose group of dexmedetomidinepretreatment can produce certain brain protective effect. But the data didnot appeared difference between the two groups.