Hinkelbein Jochen, Feldmann Robert E, Peterka Anna, Schubert Charlotte, Schelshorn Dominik, Maurer Martin H, Kalenka Armin
Clinic for Anesthesiology and Intensive Care Medicine, University of Heidelberg, Medical Faculty Mannheim, Mannheim, Germany.
Curr Neurovasc Res. 2007 Nov;4(4):280-8. doi: 10.2174/156720207782446388.
The cause of brain dysfunction during sepsis and septic encephalopathy is still under ongoing research. Sepsis induced changes in cerebral protein expression may play a significant role in the understanding of septic encephalopathy. The aim of the present study was to explore cerebral proteome alterations in septic rats. Fifty-six male Wistar rats were randomly assigned to a sepsis group (coecal ligature and puncture, CLP) or a control group (sham). Surviving rats were killed 24 or 48 hours after surgery and whole-brain lysates were used for two-dimensional gel electrophoresis and subsequent protein identification. Differentially expressed proteins were identified by mass spectrometry. Using the Ingenuity Pathways Analysis (IPA) tool, the relationship and interaction between the identified proteins was analyzed. Mortality was 53 % in septic rats. No rat of the control group was lost. More than 1,100 spots per gel were discriminated of which 29 different proteins were significantly (2-fold, P<0.01) changed: 24 proteins down-regulated after 24 hours; two proteins up-regulated and three down-regulated after 48 hours. IPA identified 11 of 35 differentially regulated proteins allocating them to an existing inflammatory pathway. In the analysis of septic rat brains, multiple differentially expressed proteins associated with metabolism, signaling, and cell stress can be identified via proteome analysis, that may help to understand the development of septic encephalopathy.
脓毒症和脓毒性脑病期间脑功能障碍的病因仍在研究中。脓毒症诱导的脑蛋白表达变化可能在理解脓毒性脑病中起重要作用。本研究的目的是探讨脓毒症大鼠的脑蛋白质组改变。56只雄性Wistar大鼠被随机分为脓毒症组（盲肠结扎和穿刺，CLP）或对照组（假手术）。存活的大鼠在手术后24或48小时处死，全脑裂解物用于二维凝胶电泳和随后的蛋白质鉴定。通过质谱鉴定差异表达的蛋白质。使用 Ingenuity Pathways Analysis（IPA）工具分析鉴定出的蛋白质之间的关系和相互作用。脓毒症大鼠的死亡率为53%。对照组无大鼠死亡。每张凝胶可分辨出1100多个斑点，其中29种不同蛋白质有显著（2倍，P<0.01）变化：24小时后24种蛋白质下调；48小时后2种蛋白质上调，3种蛋白质下调。IPA在35种差异调节蛋白质中鉴定出11种，并将它们分配到现有的炎症途径中。在脓毒症大鼠脑分析中，通过蛋白质组分析可鉴定出多种与代谢、信号传导和细胞应激相关的差异表达蛋白质，这可能有助于理解脓毒性脑病的发生发展。
