右美托咪定对体外循环大鼠脑损伤的影响

Effect of dexmedetomidine on brain injury in rats undergoing cardiopulmonary bypass

摘要:

目的 观察右美托咪定对大鼠体外循环相关脑损伤的影响。方法 将48 只健康雄性SD 大鼠随 机分为假手术组（S 组）、体外循环组（CPB 组）和右美托咪定组（Dex 组），每组16 只。S 组不进行体外循 环转流；CPB 组行体外循环转流120 min ；Dex 组泵注右美托咪定，并行体外循环转流120 min。采用ELISA 法检测不同时点血浆IL-6 因子的表达，TUNEL 检测海马CA1 区神经细胞凋亡，Western blotting 检测大鼠海 马组织cleaved Caspase-3 蛋白的表达，称重法检测大脑组织含水量。结果 与体外循环前（T0）比较，体外 循环1 h（T1）、体外循环2 h（T2）时CPB 组、Dex 组大鼠血浆IL-6 浓度升高（P <0.05）；与S 组比较，CPB 组体外循环后大鼠海马CA1 区凋亡阳性细胞和脑组织含水量增多（P <0.05），大鼠血浆IL-6 因子和海马组 织cleaved Caspase-3 蛋白表达升高（P <0.05）；与CPB 组比较，Dex 组体外循环后大鼠海马CA1 区凋亡阳性 细胞和脑组织含水量减少（P <0.05），大鼠血浆IL-6 因子和海马组织cleaved Caspase-3 蛋白表达降低（P <0.05）。 结论 右美托咪定可以减轻体外循环大鼠脑损伤，其机制可能与抑制体外循环相关的炎症反应、下调cleaved Caspase-3 蛋白表达有关。

Abstract:

Objective To investigate the effect of dexmedetomidine on attenuating apoptosis of hippocampal neurons in rats undergoing cardiopulmonary bypass (CPB). Methods Totally forty-eight Sprague Dawley male rats, weighing 250 to 350 g, were randomly divided into 3 groups (n = 16 each): sham operation group (group S), cardiopulmonary bypass group (group CPB), and dexmedetomidine group (group Dex). In group S, rats needed to be cannulated and did not undergo surgical operation for CPB, which served as sham controls, and the experiment ended after 120 min. In group CPB, all 16 rats underwent surgery to develop CPB for 120 min as model systems. Rats in group CPB did not receive any treatment, which served as CPB control (group CPB). In group Dex, rats received loading doses of dexmedetomidine 2.5 μg/kg intravenously using a microinfusion pump 15 min before CPB. Then, doses of dexmedetomidine 2.5 μg/(kg·h) were maintained intravenously during the CPB procedure for 120 min. After the experiment, rats in each group were used to detect the plasma levels of IL-6 at different time points by ELISA, neuronal apoptosis in hippocampal CA1 area by TUNEL method, the expression of cleaved Caspase-3 protein in hippocampus by Western blot and the water content of brain tissue without hippocampus by weighing method. Results In group CPB and group Dex, the expressions of IL-6 in plasma at T1 and T2 were higher than those at T0 (P < 0.05). Compared with group S, apoptosis of hippocampal neurons in CA1 region, the water content without hippocampus, the expression of IL-6 in plasma and cleaved Caspase-3 protein in hippocampus in group CPB were significantly increased after CPB (P < 0.05). Compared with group CPB, apoptosis of hippocampal neurons in CA1 region, the water content without hippocampus, the expression of IL-6 in plasma and cleaved Caspase-3 protein in hippocampus were significantly decreased in group Dex after CPB (P < 0.05). Conclusions Dexmedetomidine can reduce cerebral injury in CPB rats, and its mechanism may be related to the inhibition of inflammatory response and down regulation of the expression of cleaved Caspase-3 protein.