Muscle wasting and the temporal gene expresion pattern in a novel rat ICU model. Rattus norvegicus

Acute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. In order to elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness in AQM, gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals. Overall design: A total of five sham operated controls and 23 experimental female Sprague-Dawley rats were included in this study. The experimental rats were anaesthetized, treated with the neuromuscular blocker (NMBA), α-cobrotoxin, mechanically ventilated and monitored for durations varying from 6h to 4 days (n=13), from 5 to 9 days (n=4), and from 9 to 14 days (n=6). Muscle biopsies were obtained from gastrocnemius muscle (proximal part) immediately after euthanasia and were quickly frozen in liquid propane cooled by liquid nitrogen, and stored at -80°C.RNA was extracted.

急性四肢瘫痪性肌病（Acute quadriplegic myopathy, AQM）又称重症监护相关肌病（critical illness myopathy, CIM），在重症监护病房（intensive care unit, ICU）患者中较为常见。为阐明重症监护病房干预措施对调控AQM中肌肉萎缩与肌无力的分子及功能网络的时长依赖性影响，本研究采用模拟ICU环境的独特大鼠实验模型——即突触后麻痹、机械通气并接受全面监测的动物——在6小时至14天的多个时间点分析了基因表达谱。

实验整体设计：本研究共纳入5只假手术对照雌性斯普拉-道来大鼠（Sprague-Dawley）与23只实验雌性斯普拉-道来大鼠（Sprague-Dawley）。实验大鼠经麻醉后予以神经肌肉阻滞剂（neuromuscular blocker, NMBA）α-银环蛇毒素处理，随后实施机械通气并开展监测，监测时长分为三组：6小时至4天（n=13）、5至9天（n=4）以及9至14天（n=6）。于安乐死后即刻获取腓肠肌近端部分的肌肉活检样本，将其快速置于液氮冷却的液态丙烷中速冻，并于-80℃条件下保存，随后完成RNA提取。