右美托咪定对大鼠脑缺血再灌注时 TN F-α和 ICAM-1表达的影响

Effects of dexmedetomidine on expression of TNF-α and ICAM-1 during cerebral ischemia-reperfusion in rats

目的：评价右美托咪定对大鼠脑缺血再灌注时肿瘤坏死因子-α（TNF-α）和细胞间黏附分子-1（ICAM-1）表达的影响。方法雄性SD大鼠36只，8～12周龄，体重280～320 g ，采用随机数字表法，将其分为3组（ n＝12）：假手术组（S组）、脑缺血再灌注组（I/R组）和右美托咪定组（D组）。采用线栓法制备局灶性脑缺血再灌注损伤模型。D组在缺血即刻静脉注射右美托咪定3μg/kg，随后以3μg·kg-1·h-1速率输注120 min ，I/R组给予等容量生理盐水。分别于再灌注24、48和72 h时取4只大鼠，经左心室采集血样，检测血清S100B蛋白浓度，然后处死大鼠，取脑组织，检测TNF-α和ICAM-1的表达。结果与S组比较，I/R组和D组血清S100B蛋白浓度升高，脑组织TNF-α和ICAM-1表达上调（ P＜0.05）；与I/R组比较，D组血清S100B蛋白浓度降低，脑组织TNF-α和ICAM-1表达下调（ P＜0.05）。结论右美托咪定减轻大鼠脑缺血再灌注损伤的机制与下调TNF-α和ICAM-1表达有关。

Objective To evaluate the effects of dexmedetomidine on the expression of tumor necrosis factor-α（TNF-α） and intercellular adhesion molecule-1 （ICAM-1 ） during cerebral ischemia-reperfusion （I/R ） in rats .Methods Thirty-six male Sprague-Dawley rats , aged 8-12 weeks ,weighing 280-320 g ,were randomly divided into 3 groups （ n= 12 each ）：sham operation group （group S ） , cerebral I/R group （group I/R ） and dexmedetomidine group （group D ） .The animals were anesthetized with 10% chloral hydrate 3.5 ml/kg .The focal cerebral ischemia was induced by middle cerebral artery occlusion using a nylon thread with rounded tip inserted into internal carotid artery and advanced cranially until resistance was met .In group D ,dexmedetomidine 3μg/kg was injected intravenously immediately after beginning of ischemia ,followed by infusion at 3μg·kg-1 ·h-1 for 120 min ,while the equal volume of normal saline was given in group I/R .Four rats from each group were chosen at 24 ,48 and 72 h of reperfusion , and blood samples were taken from the left ventricle to determine the concentrations of serum S100B protein .The rats were then sacrificed and the brains were removed to determine the expression of TNF-αand ICAM-1 in brain tissues .Results Compared with group S ,the concentrations of serum S100B protein were significantly increased , and the expression of TNF-α and ICAM-1 in brain tissues was up-regulated in I/R and D groups （ P〈0.05） .Compared with group I/R ,the concentrations of serum S100B protein were significantly decreased , and the expression of TNF-α and ICAM-1 in brain tissues was down-regulated in group D （ P〈0.05 ） .Conclusion The mechanism by which dexmedetomidine reduces the cerebral I/R injury is related to down-regulation of TNF-αand ICAM-1 expression in rats .