体外循环对大鼠体内白介素．6的释放、大脑NF-κB的表达及神经认知功能的影响

背景心外科手术中，体外循环（cardiopulmonary bypass，CPB）术后发生的神经认知功能障碍一直影响着患者的生活质量。炎症反应可能是其中的因素之一。本实验中我们检测了年轻大鼠围术期体内IL-6的浓度，海马NF-κB的表达含量和神经认知功能，同时评估了氧合器的大小对上述指标的影响。方法将大鼠随机分为4组：空白对照组（n=7），假手术组（n=10，麻醉、置管、不连接体外循环）和两组体外循环实验组，CPB组大鼠在麻醉、置管后行90分钟的体外循环，分别使用小容量的大鼠氧合器（n=10）和新生儿氧合器（n=10）。在术前、CPB结束时和CPB结束后2小时采集血样检测IL-6的含量。在术后第21天采用免疫组化的方法检测海马NF—κB的表达含量。在术前和术后的21天内对神经功能采用改良孔板实验进行评估。结果CPB组与假手术组相比，IL-6的水平明显升高，新生儿氧合器组在CPB结束后2小时与大鼠氧合器组相比IL-6的水平更高[CPB／大鼠氧合器组：220pg／ml（16～415）；CPB／新生儿氧合器组：1400pg／ml（592～5812）]（P〈0．05）。3组实验组中海马NF—KB的表达含量与对照组（10±4）相比明显升高。CPB组与假手术组（173±24）相比NF．KB表达含量更高（CPB／新生儿氧合器组：271±57；CPB／大鼠氧合器组：269±72）。神经认知功能和行为学的评估结果显示组间没有差异。结论CPB引发显著的全身性炎症反应并伴随着海马中NF-κB蛋白表达的增多并没有导致神经认知功能的损伤。由此可推断，排除体外循环和炎症反应这两个因素，可能有其他因素最终导致了患者CPB术后神经认知功能的障碍。

BACKGROUND： Neurocognitive deficits after cardiac surgery with cardiopulmonary bypass （CPB） continue to affect patients ＇ quality of life, and an inflammatory reaction may be one of the contributors. We designed this experiment to study perioperative systemic interleukin-6 （IL-6） concentrations, cerebral expression of nuclear factor-kappa B （NF-κB）, and neurocognitive outcome after CPB in young rats. The impact of oxygenator size on these outcomes was also assessed. METHODS： Rats were randomly assigned to 1 of 4 groups： control （n = 7, nonanesthetized）, sham-operated rats （n = 10, anesthetized, cannulated, and not connected to CPB）, and 2 CPB groups, anesthetized, cannulated, and subiected to 90 min of CPB, using either a small-volume rat oxygenator （CPB/rat oxygenator, n = 10） or a neonate oxygenator （CPB/neonate oxygenator, n = 10）. Systemic IL-6 was determined before, at the end of, and 2 h after CPB or at equivalent times. Hippocampal NF-κB expression was assessed on postoperative day 21 using immunohistochemistry. Neurocognitive performance was assessed with the modified hole-board test at baseline and for 21 postoperative days. RESULTS： Both CPB groups had increased systemic IL-6 levels compared with sham, with the neonate oxygenator causing a substantially larger increase at 2 h after CPB compared with the rat oxygenator group （CPB/rat oxygenator： 220 pg/ml [ 16 - 415 ] ; CPB/neonate oxygenator： 1400 pg/ml [ 592 - 5812 ] ） （P 〈 0.05）. Hippocampal NF-κB was increased in experimental groups compared with controls （10 ± 4）. CPB resulted in more NF-κB- positive neurons （271 ± 57 CPB/neonate oxygenator and 269 ± 72 CPB/rat oxygenator） compared with sham operation （173 ± 24）. Neurocognitive and behavioral performances were unaltered and comparable among all groups. CONCLUSIONS： Pronounced systemic inflammatory responses to experimental CPB associated with increased hippocampal expression of NF-κB were not accompanied by neurocognitive impairment. This suggests that other factorsbeyond CPB and inflammatory responses might contribute to adverse neurocognitive outcomes after cardiac surgery.