Wan Yanjie, Xu Jing, Ma Daqing, Zeng Yinming, Cibelli Mario, Maze Mervyn
Department of Anaesthetics, Pain Medicine and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea &Westminster Hospital, London.
Anesthesiology. 2007 Mar;106(3):436-43. doi: 10.1097/00000542-200703000-00007.
Postoperative cognitive dysfunction is being increasingly reported as a complication. The authors investigated the role of cytokine-mediated inflammation within the central nervous system in the development of cognitive dysfunction in a rat model.
Adult rats were subjected to neuroleptic anesthesia (20 microg/kg fentanyl plus 500 microg/kg droperidol, intraperitoneal) for splenectomy or no surgery. On postanesthetic days 1, 3, and 7, cognitive function was assessed in a Y maze. To evaluate the immune response in the hippocampus, the authors measured glial activation, as well as transcription and expression of key proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha. To determine propensity for apoptosis, they measured expression of Bax and Bcl-2.
Cognitive function in splenectomized animals was impaired at days 1 and 3 after surgery compared with cognitive function in nonanesthetized rats. At all times, anesthetized rats that were not subjected to surgery were no different from control rats. Glial activation was observed in the hippocampus only in splenectomized rats at postsurgery days 1 and 3. Interleukin-1beta messenger RNA (mRNA) was significantly increased at postsurgery days 1 and 3, with an increase in protein expression detected on day 1. There was a significant increase in tumor necrosis factor-alpha mRNA on day 1 after surgery, although this was not associated with an increase in protein expression. The ratio of Bcl-2:Bax was significantly decreased in the splenectomized animals.
These results suggest that splenectomy performed during neuroleptic anesthesia triggers a cognitive decline that is associated with a hippocampal inflammatory response that seems to be due to proinflammatory cytokine-dependent activation of glial cells.
术后认知功能障碍作为一种并发症，其报道日益增多。作者在大鼠模型中研究了中枢神经系统内细胞因子介导的炎症在认知功能障碍发生过程中的作用。
成年大鼠接受用于脾切除术的精神安定麻醉（20微克/千克芬太尼加500微克/千克氟哌利多，腹腔注射）或不进行手术。在麻醉后第1、3和7天，通过Y迷宫评估认知功能。为评估海马体中的免疫反应，作者测量了神经胶质细胞激活以及关键促炎细胞因子白细胞介素1β和肿瘤坏死因子α的转录与表达。为确定细胞凋亡倾向，他们测量了Bax和Bcl-2的表达。
与未麻醉大鼠的认知功能相比，脾切除动物在术后第1天和第3天的认知功能受损。在所有时间点，未接受手术的麻醉大鼠与对照大鼠无差异。仅在脾切除大鼠术后第1天和第3天的海马体中观察到神经胶质细胞激活。白细胞介素-1β信使核糖核酸（mRNA）在术后第1天和第3天显著增加，在第1天检测到蛋白质表达增加。术后第1天肿瘤坏死因子-α mRNA显著增加，尽管这与蛋白质表达增加无关。脾切除动物中Bcl-2:Bax的比例显著降低。
这些结果表明，在精神安定麻醉期间进行脾切除术会引发认知功能下降，这与海马体炎症反应相关，而海马体炎症反应似乎是由于神经胶质细胞的促炎细胞因子依赖性激活所致。
