右美托咪啶对大鼠全脑缺血再灌注损伤的影响

Effects of dexmedetomidine on global cerebral ischemia-reperfusion injury in rats

目的评价右美托咪啶对大鼠全脑缺血再灌注损伤的影响。方法健康雄性SD大鼠54只，体重200—250g，采用随机数字表法，将其随机分为3组（n=18）：假手术组（S组）、缺血再灌注组（I／R组）和右美托咪啶组（D组）。I／R组和D组采用夹闭双侧颈总动脉联合低血压法建立大鼠全脑缺血再灌注损伤模型。D组于缺血再灌注即刻静脉注射右美托咪啶3,ag／kg，后以3μg·kg-1·h-1的速率静脉输注至再灌注2h。于再灌注6h（T1）、24h（T2）和72h（T1）时行神经功能缺陷评分（NDS评分），然后各组随机处死6只大鼠，取脑组织，观察海马CAI区病理学结果，采用分光光度计法测定髓过氧化物酶（MPO）活性，采用ELISA法测定TNF-α、IL-1β的含量，采用免疫组化法测定胶质纤维酸性蛋白（GFAP）表达。结果与S组比较，I／R组和D组T1-5时NDS评分、脑组织MPO活性、TNF-α和IL-113的含量升高，T2-3时GFAP表达上调（P〈0．05或0．01），海马CAl区病理学损伤明显；与I／R组比较，D组T1-5时NDS评分、脑组织MPO活性和TNF-α含量降低，T1-2时脑组织IL-1β含量降低，T2-3，时脑组织GFAP表达下调（P〈0．05或0．01），海马CAI区病理学损伤减轻。结论右美托咪啶可减轻大鼠全脑缺血再灌注损伤，其机制可能与抑制炎性反应有关。

Objective To investigate the effects of dexmedetomidine on global cerebral ischemia-reperfusion （I/R） injury in rats. Methods Fifty-four adult male SD rats weighing 200-250 g were randomly divided into 3 groups （n = 18 each）： shame operation group （group S）, global cerebral I/R group （group I/R） and dexmedetomidinc group （group D）. Global cerebral I/R was produced by occlusion of bilateral common carotid arteries combined with hypotension （MAP maintained at 35-45 mm Hg）. In group D dexmedetomidine 3μg/kg was injected iv immediately after I/R, followed by infusion of dexmedctomidine at a rate of 3 μg·kg-1·h-1 until 2 h of reperfusion. The neurological deficit score （NDS） was assessed （0 = normal, 100 = brain death） at 6 h （TI）, 24 h （T2） and 72 h （T3 ） of reperfusion, Then six rats were sacrificed in each group and brain tissues were removed for microscopic examination of hippocampus CAI region and determination of activity of mycloperoxidase （MPO）, contents of TNF-α and IL-1β and expression of glial fibrillary acidic protein （GFAP） . Results Compared with group S, NDS, MPO activity and the contents of TNF-α and IL-1βat 1β were significantly increased, the expression of GFAP was up-regulated at T2.3 in groups I/R and D （ P 〈 0.05 or 0.01）. Compared with group I/R, NDS, MPO activity and TNF-α concent were significantly decreased at T1-3 , IL-1βconcent was decreased at T1-2 , the expression of GFAP was down-regulated at T2.3 in group D （P 〈 0.05 or 0.01 ） . The pathologic changes were significantly attenuated in group D as compared with group I/R. Conclusion Dexmedetomidine can attenuate global cerebralI/R injury in rats, and the inhibition of inflammatory response may be involved in the mechanism.