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Chronic Calcineurin Inhibition via Cyclosporine A Impairs Visuospatial Learning After Isoflurane Anesthesia
背景与目的
临床研究表明，认知并发症与围手术期有关，越来越多的实验证据表明，麻醉药可以影响支撑学习和记忆的神经过程。钙调神经磷酸酶(Calcineurin)是一种钙离子依赖性磷酸酶，与突触可塑性密切相关，在吸入异氟醚后被激活，但其在麻醉的神经学反应中的作用尚不清楚。
方 法
我们研究了慢性钙调神经磷酸酶抑制对麻醉后认知功能的影响。在慢性环孢素A方案期间，对小鼠进行异氟醚麻醉30分钟的处理。测量麻醉期间的行为终点。视觉空间学习能力采用辐射状水迷宫进行评估。测定α5β3γ2γ-氨基丁酸A型受体的总蛋白和生物素化表面蛋白的表达，同时测定γ-氨基丁酸合成酶谷氨酸脱羧酶(GAD)-67的表达。
结 果
麻醉前用环孢素A处理的小鼠与假处理组和仅环孢素A处理的小鼠相比，表现出明显的视觉空间学习障碍(n=10/组，P=.0152，Tukey 事后检验 )。环孢素A并不能对视觉空间学习障碍的诱导和发生产生改变。海马蛋白表达分析显示，异氟醚处理后，GAD5GABA A型受体亚基的表面表达增加(P=.019，Dunnett事后检验)，以及GAD67的表达降低。环孢素A不能逆转这两种效应。
结 论
异氟醚通过环孢素A引起网络功能抑制性改变并排除了钙调神经磷酸酶抑制的干预。此外，我们的研究表明钙调神经磷酸酶在麻醉引起的神经反应中起着保护作用，接受环孢素A处理的患者可能是发生麻醉相关的记忆问题的高危人群。
原始文献摘要
Iris A. Speigel, Christopher M. Ma, Edyta K. Bichler. Chronic Calcineurin Inhibition via Cyclosporine A Impairs Visuospatial Learning After Isoflurane Anesthesia[J].Anesth Analg 2019;129:192–203.
BACKGROUND: Clinical studies implicate the perioperative period in cognitive complications, and increasing experimental evidence shows that the anesthetic agents can affect neuronal processes that underpin learning and memory. Calcineurin, a Ca2+-dependent phosphatase critically involved in synaptic plasticity, is activated after isoflurane exposure, but its role in the neurological response to anesthesia is unclear.
METHODS: We investigated the effect of chronic calcineurin inhibition on postanesthetic cognitive function. Mice were treated with 30 minutes of isoflurane anesthesia during a chronic cyclosporine A regimen. Behavioral end points during the perianesthesia period were quantified.
Visuospatial learning was assessed with the water radial arm maze. Total and biotinylated surface protein expression of theα5β3γ2γ-aminobutyric acid (GABA) type A receptors was measured.Expression of the GABA synthesis enzyme glutamate decarboxylase (GAD)-67 was also measured.
RESULTS: Mice treated with cyclosporine A before anesthesia showed significant deficits in visuospatial learning compared to sham and cyclosporine A–treated mice (n = 10 per group, P = .0152, Tukey post hoc test). Induction and emergence were unaltered by cyclosporine A.Analysis of hippocampal protein expression revealed an increased surface expression of the α5 GABA type A receptor subunit after isoflurane treatment (P = .019, Dunnett post hoc testing), as well as a decrease in GAD-67 expression. Cyclosporine A did not rescue either effect.
CONCLUSIONS: Our results confirm the work of others that isoflurane induces changes to inhibitory network function and exclude calcineurin inhibition via cyclosporine A as an intervention.Further, our studies suggest that calcineurin mediates a protective role in the neurological response to anesthesia, and patients receiving cyclosporine A may be an at-risk group for memory problems related to anesthesia.
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贵州医科大学高鸿教授课题组
翻译：余晓旭 编辑：何幼芹 审校：王贵龙
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