七氟醚预处理对体外循环诱发大鼠脑损伤的影响

Effect of sevoflurane preconditioning on brain injury induced by cardiopulmonary bypass in rats

目的评价七氟醚预处理对体外循环（CPB）诱发大鼠脑损伤的影响。方法SD雄性大鼠40只，6—8月龄，体重350—450g，采用随机数字表法分为5组（n=8）：假手术组（S组）、CPB组和不同浓度七氟醚预处理组（SP1组、SP2组和SP3组）。SP1组、SP2组和SP3组吸入七氟醚1h进行预处理，呼气末浓度分别为1．2％、2．4％和3．6％，然后建立CPB。分别于七氟醚预处理后转流前（T0）、CPB30min（T1）、CPB停止即刻（T2）和CPB后1、2、3h（T3-5）时，取颈静脉血样，采用ELISA法测定血清S-10013蛋白浓度。于T5时处死大鼠，取海马组织，采用TUNEL法检测神经元凋亡情况，采用免疫组织化学法检测NF—KBp65表达水平。结果与S组比较，CPB组、SP1组、SP2组和SP3组T1-5时血清S-100β蛋白浓度升高，海马凋亡神经元增多，NF—κBp65表达上调（P〈0．05）；与CPB组比较，SP1组、SP2组和SP3组T1-5时血清S-100β蛋白浓度降低，海马凋亡神经元减少，NF—κBp65表达下调（P〈0．05）；与SP1组比较，SP2和SP3组T1-5时血清S-10013蛋白浓度降低，海马凋亡神经元减少，NF—κBp65表达下调（P〈0．05）；与SP2组比较，SP3组T1-5时血清S-10013蛋白浓度降低，海马凋亡神经元减少，NF—κBp65表达下调（P〈0．05）。结论七氟醚预处理可减轻CPB诱发大鼠脑损伤，其机制可能与抑制海马神经元NF—κB的活性有关。

Objective To evaluate the effect of sevofiurane preconditioning on brain injury induced by cardiopulmonary bypass （CPB） in rats. Methods Forty adult male Sprague-Dawley rats, aged 6-8 months, weighing 350-450 g, were randomly divided into 5 groups （n= 8 each） using a random number table： sham operation group （S group） , CPB group, and preconditioning with different concentrations of sevoflurane groups （SP1, SP2 and SP3 groups）. In SP1, SP2 and SP3 groups, sevoflurane with the final concentrations of 1.2%, 2.4% and 3.6%, respectively, was inhaled for 1 h, and then CPB was started. After sevoflurane preconditioning and before CPB （T0） , at 30 min of CPB （Tl ） , at the end of CPB （ T2 ）, and at 1, 2 and 3 h after termination of CPB （T3-5 ）, venous blood samples were collected from the right internal jugular vein for determination of serum S100-β protein concentrations by enzyme-linked immunosorbent assay. Rats were sacrificed at T5, and hippocampi were isolated for determination of neuronal apoptosis （by TUNEL） and NF-KB p65 expression （by immunohistochemistry）. Results Compared with group S, the concentration of serum S100-β protein was significantly increased at T1-5, the number of apoptotic neurons was significantly increased, and the expression of NF-κB p65 was significantly up-regulated in CPB, SP1, SP2 and SP3 groups （P〈0.05）. Compared with group CPB, the serum S100-β protein concentration was significantly decreased at T1-5, the number of apoptotic neurons was significantly decreased, and the expression of NF-κB p65 was significantly down-regulated in SPI, SP2 and SP3 groups （P〈 0.05）. Compared with group SP1, the serum S100-β protein concentration was significantly decreased at T1-5, the number of apoptotic neurons was significantly decreased, and the expression of NF-κB p65 was significantly down-regulated in SP2 and SP3 groups （P〈0.05）. Compared with group SP2, the serum S100-β protein concentration was significantly decreased at T1-5, the number of apoptotic neurons was significantly decreased, and the expression of NF-κB p65 was significantly down-egulated in group SP3 （P〈0.05）. Conclusion Sevoflurane preconditioning can attenuate CPB-induced brain injury probably by inhibiting activation of NF-κB in hippocampal neurons of rats.