Experimental Researches Of Dexmedetomidine On Global Cerebral Ischemic-Reperfusion Injury In Rats

Brain is generally the most ichemic and anoxia sensitive organ.Therefore,brain will suffer a serve irreversibly damage if the ichemic time islonger than four minutes.The function of brain can not restore even bloodsupply recovers some time after cerebral ischemia.Moreover,there will appearmore serve brain dysfunction,which is called as “cerebral ischemia reperfusioninjury（CIRI）”.Many clinical diseases,especially in neurosurgery,cardiac andvascular surgery,the elderly surgery and the treatment of critically illpatients,are facing the risk of cerebral ischemia.Mental and exercise disorderscaused by ichemic damage seriously affect people′s quality of life and bringgreat economic burden to families and society.Therefore,how to reduce theperioperative ichemic complications has become a problem needed to dealwith in clinical practice.Dexmedetomidine is a novel highly selective and specificity α2-adrenoceptor agonist,it offers beneficial pharmacological properties,providing dose-dependent sedation, analgesia,anxiolysis, sympatholysis andwithout relevant respiratory depression.It was approved for adult sedation andanalgesia use in the intensive care unit （ICU） by Food and DrugAdministration （FDA）in the USA in1999.In China,FDA approved it forinduction in general anesthesia and sedation in mechanical ventilation in2009.Foreign studies have reported that dexmedetomidine has a protectiveeffect on cerebral ischemic injury,which may be related to the reducion ofextracellular catecholamine levels and excitatory neurotransmitterglutamate,and the regulation of apoptosis.However,the exact mechanism hasnot yet clarified.In this experiment,we maked the modal of global cerebral ischemia byfour-vessel occlusion method,the effects of dexmedetomidine with different doses were observed.The possible mechanism was explored from the freeradical damage and inflammatory response.Objective：The protective effect of dexmedetomidine on the brains of ratson CIRI is investigated by evaluating the motor function,detecting the brainwater content,measuring MDA content and SOD activity in brain tissue,measuring the concentration of S100B protein and levels of inflammatoryfactors TNF-alpha, IL-1β in serum.Methods：Male SD rats,aged8-12weeks,weighing180-320g,were used inthis study. Global cerebral ischemic-reperfusion was induced by four-vesselocclusion.Forty rats of successful model were randomly divided into5groups(n=8each): sham operation group(group S);ischemic-reperfusioncontrol group(group C);low,median and high doses of dexmedetomidinegroups(group D1-3).In group D1-3,immediately after ischemic,dexmedetomidine0.05,0.5and5μg·kg-1·min-1were infused over2hrespectively,while normal saline2ml/h were given instead ofdexmedetomidine in group S and C.The motor activity tests(beam-walkingtest and pull-up test) were carried out24h after reperfusion. The brain watercontent was detected by wet and dry weight method.Then blood samples weretaken for measurement of plasma concentration of S-100B and inflammatoryfactors TNF-alpha, IL-1β by ELISA.The rats were killed and brain tissueswere taken for determination of the concentration of MDA and activity ofSOD by thiobarbituric acid and xanthine oxidase.Results：Compared with group S,the motor activitives and SOD activitywere significantly decreased, concentrations of S-100B and MDA weresignificantly increased,levels of inflammatory factors TNF-alpha, IL-1βwere significantly rised in group C and D1-3(P<0.05). Compared with group C,the motor activity was significantly improved in group D1(P<0.05). Theconcentrations of S-100B and MDA were significantly decreased andactivitives of SOD were increased in D1and D2(P<0.05).The levels ofinflammatory factors TNF-alpha, IL-1β were significantly descented in groupD1-3(P<0.05). All the experimental parameters are the most notable changed in groupD1(P<0.05).Conclusions： Dexmedetomidine has a neuroprotective effect againstglobal cerebral ischemia-reperfusion injury in rats. It can improve the motorfunction and the antioxidant capacity of brain tissue,maintain the integrity ofglial cells and inhibit the inflammatory response.The suitable concentration is0.05μg·kg-1·min-1,large dose of dexmedetomidine does not show the relevantneuroprotective effect.