Department of Anaesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, PR China.
Neurosci Lett. 2009 Nov 13;465(2):165-70. doi: 10.1016/j.neulet.2009.08.025. Epub 2009 Aug 12.
Cognitive dysfunction after propofol anesthesia has been previously found. The underlying mechanisms of this sequel remain unclear. Insoluble proteins as major targets of anesthetics participated in various pathophysiological processes. This study aimed to provide evidence that changes in insoluble proteome in rat hippocampus may be involved in molecular mechanism of cognitive dysfunction following propofol anesthesia. Proteins extracted from rat hippocampus were separated by two-dimensional electrophoresis (2-DE). Their expression patterns were observed at 1, 6, 24 h and 7 days after 3 h of propofol anesthesia. Differentially expressed protein spots among groups were submitted to matrix-assisted laser desorption/ionization time of flight mass spectrometer (MALDI-TOF MS) assay and peptide mass fingerprinting (PMF) identification. Identified proteins were further analyzed through Gene Ontology (GO). Results of 2-DE were selectively assayed using Western blot and RT-PCR. Fifty-nine differentially expressed proteins were detected, among which 43 were identified through MALDI-TOF MS. Most identified proteins were distributed in organelles and membranes. According to biological process category, 27 proteins were involved in metabolic process, 19 in developmental process, 14 in stimulus-response, and 21 in biological regulation. Most changes took place within 24 h, with more down-regulation within 6 h. Twelve proteins did not restore to the basic level until the 7th day after propofol anesthesia. Expressions of insoluble proteome dynamically changed following propofol anesthesia. Down-regulations at early stage might produce depressive effects, which may be involved in molecular mechanism of cognitive dysfunction after propofol anesthesia.
先前已经发现丙泊酚麻醉后会出现认知功能障碍。这种后遗症的潜在机制尚不清楚。不可溶性蛋白作为麻醉剂的主要靶标，参与了各种病理生理过程。本研究旨在提供证据表明，大鼠海马中不可溶性蛋白质组的变化可能参与了丙泊酚麻醉后认知功能障碍的分子机制。从大鼠海马中提取蛋白质，通过二维电泳（2-DE）进行分离。在丙泊酚麻醉 3 小时后 1、6、24 小时和 7 天观察其表达模式。组间差异表达的蛋白斑点进行基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）分析和肽质量指纹图谱（PMF）鉴定。通过基因本体论（GO）进一步分析鉴定的蛋白质。使用 Western blot 和 RT-PCR 选择性检测 2-DE 的结果。检测到 59 个差异表达的蛋白质，其中 43 个通过 MALDI-TOF MS 鉴定。大多数鉴定的蛋白质分布在细胞器和膜中。根据生物过程类别，27 个蛋白质参与代谢过程，19 个参与发育过程，14 个参与刺激反应，21 个参与生物调节。大多数变化发生在 24 小时内，6 小时内下调更为明显。直到丙泊酚麻醉后第 7 天，才有 12 种蛋白质未恢复到基础水平。丙泊酚麻醉后不可溶性蛋白质组的表达发生动态变化。早期的下调可能会产生抑郁作用，这可能与丙泊酚麻醉后认知功能障碍的分子机制有关。
