Tsuboko Yoshiaki, Sakamoto Atsuhiro
Department of Anaesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Biomed Res. 2011 Feb;32(1):55-65. doi: 10.2220/biomedres.32.55.
Previous studies suggest that propofol and sevoflurane anaesthesia in rats may have variable effects on the proteome. Brains from untreated rats and rats anaesthetised with intravenous propofol infusion or inhaled sevoflurane were collected at various time points post-anaesthesia and subjected to global protein expression profiling using two-dimensional gel electrophoresis. Significant changes in protein spot intensity (i.e. expression) between the propofol and sevoflurane groups demonstrated clear similarities and differences in proteomic regulation by these anaesthetics. The proteins regulated were broadly classified into groups involved in cytoskeletal/neuronal growth, cellular metabolism, signalling, and cell stress/death responses. Proteins concerned with cell death and stress responses were down-regulated by both agents, but the anaesthetics had variable effects on proteins in the other groups. Importantly, proteins such as Ulip2 and dihydropyrimidinase-like-2 were regulated in opposite directions by propofol and sevoflurane. Moreover, the time-course of regulation of proteins varied depending on the agent used. These data suggest different underlying mechanisms of proteomic regulation. We found that sevoflurane anaesthesia had more pronounced effects, on a wider range of proteins, and over an apparently longer duration than propofol. Thus, sevoflurane could be considered a more disruptive anaesthetic agent. Our findings show that protein expression is regulated differentially according to the anaesthetic agent and the method of delivery support and extend our previous observations of differential genomic regulation by anaesthetics in the brain. This study highlights the power of proteomic studies in assessing the effects of certain anaesthetics on the integrity of neuronal structure and function.
先前的研究表明，大鼠使用丙泊酚和七氟醚麻醉可能对蛋白质组产生不同的影响。在麻醉后的不同时间点收集未处理大鼠以及静脉输注丙泊酚或吸入七氟醚麻醉的大鼠的大脑，并用二维凝胶电泳对其进行整体蛋白质表达谱分析。丙泊酚组和七氟醚组之间蛋白质斑点强度（即表达）的显著变化表明，这些麻醉剂在蛋白质组调控方面存在明显的异同。所调控的蛋白质大致分为参与细胞骨架/神经元生长、细胞代谢、信号传导以及细胞应激/死亡反应的几类。与细胞死亡和应激反应相关的蛋白质在两种麻醉剂作用下均下调，但麻醉剂对其他组中的蛋白质有不同影响。重要的是，诸如Ulip2和二氢嘧啶酶样-2等蛋白质在丙泊酚和七氟醚作用下呈相反方向调控。此外，蛋白质调控的时间进程因所用麻醉剂而异。这些数据表明蛋白质组调控存在不同的潜在机制。我们发现，与丙泊酚相比，七氟醚麻醉对更广泛的蛋白质有更显著的影响，且持续时间明显更长。因此，七氟醚可被视为一种更具干扰性的麻醉剂。我们的研究结果表明，蛋白质表达根据麻醉剂和给药方式的不同而受到不同调控，这支持并扩展了我们之前关于麻醉剂对大脑基因组差异调控的观察结果。这项研究突出了蛋白质组学研究在评估某些麻醉剂对神经元结构和功能完整性影响方面的作用。
