右美托咪定对全脑缺血再灌注大鼠血脑屏障通透性的影响

Effect of dexmedetomidine on permeability of blood-brain barrier in rats subjected to global cerbral ischemia-reperfusion

目的评价右美托咪定对全脑缺血再灌注大鼠血脑屏障通透性的影响。方法成年雄性sD大鼠36只，体重250—300g，采用随机数字表法，将其分为3组（n=12）：假手术组（S组）、全脑缺血再灌注组（I／R组）和右美托咪定组（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组于再灌注即刻经颈总静脉注射右美托咪定3μg／kg负荷剂量，后以3μg·kg^-1·h^-1的速率静脉输注至再灌注2h。再灌注24h时，处死大鼠，取脑组织，观察海马CA1区病理学结果，测定细胞凋亡水平、脑含水量、脑组织伊文氏蓝（EB）含量和水通道蛋白4（AQP4）的表达。结果与s组比较，I／R组和D组细胞凋亡增加，脑含水量和脑组织EB含量升高，AQP4表达上调（P〈0．05或0．01）；与I／R组比较，D组细胞凋亡减少，脑含水量和脑组织EB含量降低，AQP4表达下调（P〈0．05或0．01），病理学损伤减轻。结论右美托咪定可降低血脑屏障通透性，减轻大鼠全脑缺血再灌注损伤，其机制可能与下调AQP4的表达有关。

Objective To evaluate the effects of dexmedetomidine on the permeability of blood-brain barrier in rats subjected to global cerebral ischemia-reperfusion （I/R）. Methods Thirty-six male Spragne-Dawley rats, weighing 250-300 g, were randomly divided into 3 groups （n = 12 each） ： sham operation group （group S）, global cerebral I/R group （group I/R） and dexmedetomidine group （group D）. Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension （MAP was maintained at 35-45 mm Hg） in anesthetized rats. In group D, dexmedetomidine was infused at a rate of 3μg·kg- 1·h^-1 until 2 h of reperfusion after a loading dose of dexmedetomidine 3μg/kg was injected intravenously immediately after onset of I/R. The rats were sacrificed at 24 h of reperfusion and their brains were immediately removed for microscopic examination of hippocampal CA1 region and for determination of the cell apoptosis, brain water content, Evans blue content and aquaporin 4 （AQP4） expression. Results The number of apoptotic cells was significantly larger, and brain water content, Evans blue content and AQP4 expression were higher in groups I/R and D than in group S （ P 〈 0.05 or 0.01 ）. The number of apoptotic cells was significantly smaller, and brain water content, and Evans blue content and AQP4 expression were lower in group D than in group I/R （ P 〈 0.05 or 0.01 ）. Global cerebral I/R-induced pathological changes were significantly attenuated in group D. Conclusion Dexmedetomidine can decrease the permeability of blood-brain barrier and attenuate global cerebral I/R injury in rats, and down-regulation of AQP4 expression may be involved in the mechanism.