Body temperature and mouse scoring systems as surrogate markers of death in cecal ligation and puncture sepsis.
Body temperature and mouse scoring systems as surrogate markers of death in cecal ligation and puncture sepsis.
复制标题
DOI：
10.1186/s40635-018-0184-3
复制
发表时间：
2018-07-27
影响因子：
3.5
通讯作者：
Liaw PC
中科院分区：
文献类型：
--
作者：
Mai SHC;Sharma N;Kwong AC;Dwivedi DJ;Khan M;Grin PM;Fox-Robichaud AE;Liaw PC
尽管进行动物研究的伦理标准越来越高，但在小鼠败血症研究中，死亡仍然经常被用作终点。最近，小鼠脓毒症评分（MSS）、小鼠脓毒症临床评估评分（M-CASS）和小鼠鬼脸量表（MGS）被开发为评估小鼠疼痛和疾病严重程度的替代终点评分系统。本研究的目的是比较这些评分系统和体温监测在盲肠结扎和穿刺（CLP）脓毒症模型中预测疾病进展和死亡的有效性，以便更好地为实验性脓毒症死亡替代终点的选择提供信息。C57Bl/6J小鼠进行对照假手术，或中度或重度CLP脓毒症。使用改良版的MSS、M-CASS和MGS评分系统，每4小时监测一次所有小鼠的替代死亡标志物，直到术后24小时，或直到终点（无法行走）和随后的安乐死。30%的中度CLP小鼠在CLP后24小时达到终点，而100%的重度CLP小鼠在20小时内达到终点。改良的MSS， M-CASS和MGS评分均升高，而体温下降，以时间依赖和脓毒症严重程度依赖的方式，尽管改良的M-CASS评分显示出很大的可变性。受试者工作特征曲线显示，最后记录的体温（AUC = 0.88, 95% CI 0.77-0.99）、体温变化（AUC = 0.89, 95% CI 0.78 - 0.99）、改良的M-CASS （AUC = 0.93, 95% CI 0.85-1.00）和改良的MSS （AUC = 0.95, 95% CI 0.88 - 1.01）评分对于预测CLP脓毒症的死亡均具有稳健性，而改良的MGS （AUC = 0.78, 95% CI 0.63-0.92）的稳健性较差。改良后的MSS和体温是评估CLP模型中疾病严重程度和预测死亡的有效标志物，因此应被视为有效的替代标志物，以取代死亡作为小鼠CLP败血症研究的终点。
Despite increasing ethical standards for conducting animal research, death is still often used as an endpoint in mouse sepsis studies. Recently, the Murine Sepsis Score (MSS), Mouse Clinical Assessment Score for Sepsis (M-CASS), and Mouse Grimace Scale (MGS) were developed as surrogate endpoint scoring systems for assessing pain and disease severity in mice. The objective of our study was to compare the effectiveness of these scoring systems and monitoring of body temperature for predicting disease progression and death in the cecal ligation and puncture (CLP) sepsis model, in order to better inform selection of surrogate endpoints for death in experimental sepsis. C57Bl/6J mice were subjected to control sham surgery, or moderate or severe CLP sepsis. All mice were monitored every 4 h for surrogate markers of death using modified versions of the MSS, M-CASS, and MGS scoring systems until 24 h post-operatively, or until endpoint (inability to ambulate) and consequent euthanasia. Thirty percent of mice subjected to moderate severity CLP reached endpoint by 24 h post-CLP, whereas 100% undergoing severe CLP reached endpoint within 20 h. Modified MSS, M-CASS, and MGS scores all increased, while body temperature decreased, in a time-dependent and sepsis severity-dependent manner, although modified M-CASS scores showed substantial variability. Receiver operating characteristic curves demonstrate that the last recorded body temperature (AUC = 0.88; 95% CI 0.77–0.99), change in body temperature (AUC = 0.89; 95% CI 0.78–0.99), modified M-CASS (AUC = 0.93; 95% CI 0.85–1.00), and modified MSS (AUC = 0.95; 95% CI 0.88–1.01) scores are all robust for predicting death in CLP sepsis, whereas modified MGS (AUC = 0.78; 95% CI 0.63–0.92) is less robust. The modified MSS and body temperature are effective markers for assessing disease severity and predicting death in the CLP model, and should thus be considered as valid surrogate markers to replace death as an endpoint in mouse CLP sepsis studies.