Wong J P, Saravolac E G, Clement J G, Nagata L P
Medical Countermeasures Section, Defence Research Establishment Suffield, Alberta, Canada.
Lab Anim Sci. 1997 Apr;47(2):143-7.
A hypothermia model was developed to predict mortality and morbidity caused by respiratory influenza virus infection in mice. To increase virulence, egg-propagated influenza A/PR/8 virus was adapted for growth in mice by four blind serial passages. The mouse-adapted influenza A virus was then used to infect groups of BALB/c mice via the intranasal route, and the 50% lethal dose (LD50) was determined. Rectal temperature of the infected mice was monitored daily, and survival rate was determined at day 14 after infection. The lowest average body temperature recorded in infected mice was approximately 10 degrees C below that in noninfected mice. In mice that developed hypothermia, with body temperature of 32 degrees C or lower, morbidity and mortality inevitably occurred. In this study, the LD50 and the 50% hypothermia-inducing dose (HID50) for mouse-adapted influenza A virus were compared and calculated to be at the same dose. These results suggest that the HID50 model could be used to predict mortality and morbidity associated with influenza virus infection in mice. This model could potentially be used to substantially reduce the time and extent of suffering inflicted on experimental animals due to viral infections, and therefore may serve as a more humane alternative to LD50 determinations.
建立了一种体温过低模型，以预测小鼠感染呼吸道流感病毒所致的死亡率和发病率。为提高病毒毒力，通过四次盲传将鸡胚传代的甲型流感病毒A/PR/8株适应于在小鼠体内生长。然后，用适应小鼠的甲型流感病毒经鼻内途径感染BALB/c小鼠组，并测定50%致死剂量（LD50）。每天监测感染小鼠的直肠温度，并在感染后第14天测定存活率。感染小鼠记录到的最低平均体温比未感染小鼠低约10摄氏度。在体温过低（体温为32摄氏度或更低）的小鼠中，不可避免地会出现发病和死亡情况。在本研究中，对适应小鼠的甲型流感病毒的LD50和50%体温过低诱导剂量（HID50）进行了比较，计算得出二者剂量相同。这些结果表明，HID50模型可用于预测小鼠流感病毒感染相关的死亡率和发病率。该模型有可能大幅减少病毒感染给实验动物带来的痛苦时间和程度，因此可作为LD50测定的一种更人道的替代方法。
