Wang Zhen, Zhou Zhengwei, Guo Paipai, Wang Manman, Sun Hanfei, Tai Yu, Xiao Feng, Han Yongsheng, Wei Wei, Wang Qingtong
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, China.
Department of Emergency Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Exp Physiol. 2021 Apr;106(4):868-881. doi: 10.1113/EP089228. Epub 2021 Feb 16.
What is the central question of this study? Do normal adult DBA/1 mice have cardiac function and performance equal to those of C57BL/6J mice? What is the main finding and its importance? Male adult DBA/1 mice show equivalent cardiac function to C57BL/6J mice up to 8 months old. Therefore, cardiac dysfunction could be investigated in an autoimmune diseases model established with DBA/1 mice.
Cardiovascular mortality has been increasing, and in particular, cardiovascular damage caused by some chronic autoimmune diseases accounts for a large proportion of this. C57BL/6J mice have been used mostly in studies of cardiovascular diseases. However, for purposes of modelling, this strain of mouse has a very low incidence of some chronic immune diseases such as rheumatoid arthritis, to which instead DBA/1 mice are more susceptible. Basic cardiac function differs between mice with different genetic backgrounds. Therefore, we monitored cardiac function and structure of normal male C57BL/6J and DBA/1 mice for six consecutive months. Echocardiography was used to monitor cardiac functions once a month and cardiac systolic function was measured upon isoproterenol challenge at the end of observation. The Excitation-contraction coupling-related proteins were measured by western blotting. Heart tissue sections were subject to haematoxylin-eosin, TUNEL and Alizarin red staining. The results demonstrated that systolic and diastolic function did not vary significantly and both strains were indistinguishable in appearance and structure of hearts. DBA/1 mice showed a good cardiac β-adrenergic response comparable to C57BL/6J mice with isoproterenol treatment. The phosphorylation of phospholamban at either its protein kinase A or its Ca /calmodulin-dependent protein kinase II site, as well as the activation of troponin I showed no significant difference between strains. These findings suggested that there was no obvious difference in the heart structure and function of normal male DBA/1 mice compared with C57BL/6J mice. The DBA/1 mouse is a strain applicable to investigating autoimmune disease-induced heart dysfunction and exploring potential interventions.
本研究的核心问题是什么?正常成年DBA/1小鼠的心脏功能和性能是否与C57BL/6J小鼠相同?主要发现及其重要性是什么?雄性成年DBA/1小鼠在8个月大之前心脏功能与C57BL/6J小鼠相当。因此,可以在以DBA/1小鼠建立的自身免疫性疾病模型中研究心脏功能障碍。
心血管疾病死亡率一直在上升,尤其是一些慢性自身免疫性疾病导致的心血管损害占了很大比例。C57BL/6J小鼠大多用于心血管疾病研究。然而,出于建模目的,该品系小鼠对某些慢性免疫疾病(如类风湿性关节炎)的发病率非常低,而DBA/1小鼠对这些疾病更易感。不同遗传背景的小鼠基本心脏功能存在差异。因此,我们连续六个月监测正常雄性C57BL/6J和DBA/1小鼠的心脏功能和结构。每月使用超声心动图监测心脏功能一次,并在观察结束时用异丙肾上腺素激发后测量心脏收缩功能。通过蛋白质印迹法测量兴奋-收缩偶联相关蛋白。心脏组织切片进行苏木精-伊红、TUNEL和茜素红染色。结果表明,收缩和舒张功能没有显著差异,两种品系在心脏外观和结构上没有区别。经异丙肾上腺素处理后,DBA/1小鼠显示出与C57BL/6J小鼠相当的良好心脏β-肾上腺素能反应。受磷蛋白在蛋白激酶A或钙/钙调蛋白依赖性蛋白激酶II位点的磷酸化以及肌钙蛋白I的激活在品系间没有显著差异。这些发现表明,正常雄性DBA/1小鼠与C57BL/6J小鼠相比,心脏结构和功能没有明显差异。DBA/1小鼠是一种适用于研究自身免疫性疾病引起的心脏功能障碍和探索潜在干预措施的品系。