Optimization of a Rhabdomyolysis Model in Mice With Exertional Heat Stroke Mouse Model of EHS-Rhabdomyolysis
Optimization of a Rhabdomyolysis Model in Mice With Exertional Heat Stroke Mouse Model of EHS-Rhabdomyolysis
复制标题
劳力性中暑小鼠横纹肌溶解模型的优化 EHS-横纹肌溶解小鼠模型
DOI：
10.3389/fphys.2020.00642
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发表时间：
2020-06-16
影响因子：
4
通讯作者：
Ma, Qiang
中科院分区：
文献类型：
--
作者：
He, Si-Xiao;Li, Ru;Ma, Qiang
中暑（EHS）是一种危及生命的疾病，其特征是高死亡率和横纹肌溶解症（RM）的发生率。因此，建立一种能准确反映EHS患者临床特征的稳定的RM模型，为进一步研究RM的发病机制提供客观的动物模型，具有重要的临床意义。本研究选用8 ~ 9周龄、雄性、野生型C57 BL/6 J小鼠，在性成熟阶段，随机分为4组：EHS组、经典中暑组（CHS）、假热运动组和假热休息组。在相对高水平的温度和湿度（37.5°C，65%相对湿度（RH）; 37.5°C，70%RH; 39.5°C，65%RH;和39.5°C，70%RH）以及高核心温度（Tc; 42、42.5和43°C）下测定小鼠的存活率。结果表明：39.5°C和65%RH的环境条件最适合EHS建模。EHS评估的终点是疲惫或个体的核心温度达到43°C。在这些条件下，EHS组小鼠在24小时内的存活率为37.34%，这与EHS患者的高死亡率特征一致。HE染色和透射电镜观察显示EHS组有严重的RM。EHS组肌酸激酶水平大多超过10，000 U/L，约为假热休息组的10倍。EHS组的肾小管表现出严重的坏死，并且使用活体双光子显微镜也观察到该组骨骼肌中的钙超载。综上所述，我们对EHS诱导的RM动物模型进行了改进，以真实反映EHS患者的临床特征。这一新的动物模型将有助于进一步研究RM的发病机制。
Exertional heat stroke (EHS) is a life-threatening disease characterized by high mortality and incidence of rhabdomyolysis (RM). It would therefore be valuable to establish a stable EHS-induced RM model that accurately reflects the clinical characteristics of EHS patients and provides an objective animal model for further study of the pathogenesis of RM. In the current study, 8∼9-week-old, male, wild-type C57BL/6J mice, at the stage of sexual maturity, were randomly divided into four groups: the EHS group, the classical heat stroke (CHS) group, the sham heat exercise group, and sham heat rest group. The survival rate of mice was determined under relatively high levels of temperature and humidity (37.5°C, 65% relative humidity (RH); 37.5°C, 70% RH; 39.5°C, 65% RH; and 39.5°C, 70% RH) as well as a high core temperature (Tc; 42, 42.5, and 43°C). Results showed that the environmental condition of 39.5°C and 65% RH was most suitable for EHS modeling. The end point of EHS evaluation was exhaustion or an individual’s core temperature reaching 43°C. The survival rate of mice in the EHS group within 24 h under these conditions was 37.34%, which is consistent with the high mortality characteristics noted in EHS patients. Severe RM was observed in the EHS group by H&E staining and transmission electron microscopy. Creatine kinase levels in the EHS group mostly exceeded 10,000 U/L, which was approximately 10 times higher than that in the sham heat rest group. Renal tubules of the EHS group exhibited severe necrosis, and calcium overload in the skeletal muscles of this group was also observed using intravital 2-photon microscopy. In conclusion, we made improvements to a stable EHS-induced RM animal model to truly reflect the clinical characteristics of EHS patients. This new model should be helpful in the further study of RM pathogenesis.