Kanda T, Koike H, Arai M, Wilson J E, Carthy C M, Yang D, McManus B M, Nagai R, Kobayashi I
Department of Laboratory Medicine, Gunma University School of Medicine, Gunma University, Maebashi, Japan.
Int J Cardiol. 1999 Jan;68(1):13-22. doi: 10.1016/s0167-5273(98)00250-2.
The role of lymphocytes in the pathogenesis of viral myocarditis is controversial. To better understand how lymphocyte maturation controls a virus-induced myocarditic process, a murine model of viral myocarditis was utilized. Encephalomyocarditis virus (EMCV) was inoculated intraperitoneally into three kinds of mice; virus-susceptible C57BL/6, virus-resistant 129/SV and recombination activity gene (RAG)-2 knockout 129/SV mice. The RAG2 participate in the maturity of T and B lymphocytes. Survival rate, heart weight (HW), HW to body weight (BW) ratio, viral genome, cardiac inflammation and myocardial necrosis were evaluated after EMCV (500 plaque forming unit/mouse) inoculation. On post-inoculation day 10, the survival rate of C57BL/6, 129/SV and RAG2 knockout mice were 42, 90 and 0%, respectively. Myocardial viral titer was significantly (P<0.05) higher in C57BL/6 and RAG2 knockout mice than in 129/SV mice. In situ hybridization demonstrated the EMCV genome in the myocardium of RAG2 knockout and C57BL/6 mice, but not in 129/SV mice. At day 8, HW and HW/BW ratios were elevated (P<0.05) in RAG2 knockout mice as well as C57BL/6 mice compared with 129/SV mice. Myocardial necroses were more severe in RAG2 knockout mice than in wild-type 129/SV mice. In conclusion, matured lymphocytes protect the development of viral myocarditis which includes viral replication and myocardial apoptosis.
淋巴细胞在病毒性心肌炎发病机制中的作用存在争议。为了更好地理解淋巴细胞成熟如何控制病毒诱导的心肌炎过程，我们利用了病毒性心肌炎的小鼠模型。将脑心肌炎病毒（EMCV）腹腔注射到三种小鼠体内；病毒易感的C57BL/6小鼠、病毒抗性的129/SV小鼠和重组激活基因（RAG）-2敲除的129/SV小鼠。RAG2参与T和B淋巴细胞的成熟。在接种EMCV（500个噬斑形成单位/小鼠）后，评估存活率、心脏重量（HW）、心脏重量与体重（BW）之比、病毒基因组、心脏炎症和心肌坏死情况。在接种后第10天，C57BL/6、129/SV和RAG2敲除小鼠的存活率分别为42%、90%和0%。C57BL/6和RAG2敲除小鼠心肌中的病毒滴度显著（P<0.05）高于129/SV小鼠。原位杂交显示RAG2敲除小鼠和C57BL/6小鼠的心肌中有EMCV基因组，但129/SV小鼠中没有。在第8天，与129/SV小鼠相比，RAG2敲除小鼠以及C57BL/6小鼠的HW和HW/BW比值升高（P<0.05）。RAG2敲除小鼠的心肌坏死比野生型129/SV小鼠更严重。总之，成熟的淋巴细胞可保护病毒性心肌炎的发展，包括病毒复制和心肌细胞凋亡。
