Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Cardiovasc Pathol. 2013 Jan-Feb;22(1):96-101. doi: 10.1016/j.carpath.2012.06.004. Epub 2012 Jul 10.
C57BL/6 mice have been considered resistant to cardiotropic coxsackievirus B3 (CVB3)-induced myocarditis. However, establishment of viral myocarditis model in C57BL/6 mouse is still a necessity. Here, we discuss the effects of mouse initial body weight and different virus inoculation doses on the onset of acute viral myocarditis in C57BL/6 mouse.
According to initial body weight, mice were grouped into group A (3-4 weeks, 11-15 g) and group B (5-6 weeks, 18-20 g). Then, each group was divided into three subgroups inoculated with different virus doses: 1000 50% tissue culture infectious dose (TCID(50))/ml, 10,000 TCID(50)/ml, and 100,000 TCID(50)/ml. Virus existence and myocardium inflammatory infiltration conditions were observed and evaluated 7 days postinfection.
Immunohistochemistry staining showed that virus capsid protein VP1 appeared in the myocardia of virus-infected mice. Three subgroups in the lower-body-weight group (group A) came out with a higher mortality (40%-100%), while the higher-body-weight group (group B) showed a tendency for body weight decline. Histopathologically, myocardia of the survival cases in the lower-initial-body-weight group got inflammatory infiltration, while almost no inflammation appeared in the dead cases. In the higher-body-weight group, myocardium inflammatory infiltration deteriorated with the increase of virus doses and bared a relatively sound survival rate.
This study indicated that the initial body weight and virus infection dose are two factors affecting the onset of viral myocarditis in C57BL/6 mice. Accordingly, initial body weight of 18-20 g and an inoculation dose of 100,000 TCID(50)/ml × 0.3 ml CVB3 might be an optimal choice to induce acute viral myocarditis in C57BL/6 mice.
C57BL/6 小鼠被认为对亲心性柯萨奇病毒 B3（CVB3）诱导的心肌炎具有抗性。然而，建立 C57BL/6 小鼠的病毒性心肌炎模型仍然是必要的。在这里，我们讨论了小鼠初始体重和不同病毒接种剂量对 C57BL/6 小鼠急性病毒性心肌炎发病的影响。
根据初始体重，将小鼠分为 A 组（3-4 周，11-15 g）和 B 组（5-6 周，18-20 g）。然后，每组再分为三个亚组，接种不同剂量的病毒：1000 50%组织培养感染剂量（TCID(50)）/ml、10000 TCID(50)/ml 和 100000 TCID(50)/ml。感染后第 7 天观察和评估病毒存在和心肌炎症浸润情况。
免疫组织化学染色显示，病毒衣壳蛋白 VP1 出现在感染病毒的小鼠心肌中。低体重组（A 组）的三个亚组死亡率较高（40%-100%），而高体重组（B 组）体重下降趋势。组织病理学检查显示，低初始体重组存活病例的心肌有炎症浸润，而死亡病例几乎没有炎症。在高体重组中，随着病毒剂量的增加，心肌炎症浸润加重，存活率相对较高。
本研究表明，初始体重和病毒感染剂量是影响 C57BL/6 小鼠病毒性心肌炎发病的两个因素。因此，初始体重为 18-20 g，接种 CVB3 100000 TCID(50)/ml×0.3 ml 可能是诱导 C57BL/6 小鼠急性病毒性心肌炎的最佳选择。
