Colston J T, Chandrasekar B, Freeman G L
Division of Cardiology, University of Texas Health Science Center at San Antonio, USA.
Cardiovasc Res. 1998 Apr;38(1):158-68. doi: 10.1016/s0008-6363(97)00323-4.
The extent to which apoptosis contributes to myocyte cell loss during acute carditic viral infection is unknown. To assess whether apoptosis occurs in acute viral myocarditis, and how it is modulated, we studied mice inoculated with coxsackievirus B3 (CVB3).
Five CD1 and C3H.HeJ (C3H) mice/group were sacrificed as saline vehicle-injected controls, and at 1, 2, and 3 weeks post-inoculation (p.i.) with 5 x 10(6) pfu CVB3. Histopathological status and terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assays quantified inflammation, necrosis and apoptosis in myocardium. Apoptosis-related protein immunoreactivity defined presence and location of Bax, Fas, Fas Ligand (FasL), Bcl-2, interleukin-1 beta converting enzyme (ICE), inducible nitric oxide synthase (iNOS) and the proto-oncogene p53.
Both strains exhibited significant histopathology at all time points. Saline-injected control animals showed no signs of inflammation and no significant difference in apoptosis-related protein immunoreactivity was observed between strains. Myocardial TUNEL-positive cells were exceedingly rare though apoptosis was present in thymic medulla and spleen follicles. Pro-apoptotic proteins Bax, Fas, and FasL were present in all groups though no clear correlation with histopathology was apparent. By contrast, the anti-apoptotic protein Bcl-2 showed mild immunoreactivity in controls, which increased following infection and correlated well with histopathological scores in both strains. Myocardial iNOS immunoreactivity displayed a similar though weaker staining pattern to Bcl-2 over the 3 week study period in both strains. Neither ICE nor p53 immunoreactivity could be demonstrated in myocardium.
Thus, despite marked inflammatory activity, myocyte apoptosis is rare in acute CVB3 myocarditis in CD1 and C3H.HeJ mice.
凋亡在急性感染性病毒性心肌炎期间导致心肌细胞丢失的程度尚不清楚。为了评估急性病毒性心肌炎中是否发生凋亡以及其如何被调控，我们研究了接种柯萨奇病毒B3（CVB3）的小鼠。
每组5只CD1和C3H.HeJ（C3H）小鼠作为注射生理盐水的对照，在接种5×10⁶空斑形成单位CVB3后的第1、2和3周处死。组织病理学状态和末端转移酶介导的dUTP-生物素缺口末端标记（TUNEL）分析对心肌中的炎症、坏死和凋亡进行定量。凋亡相关蛋白免疫反应性确定了Bax、Fas、Fas配体（FasL）、Bcl-2、白细胞介素-1β转化酶（ICE）、诱导型一氧化氮合酶（iNOS）和原癌基因p53的存在和位置。
在所有时间点，两个品系均表现出明显的组织病理学变化。注射生理盐水的对照动物未显示炎症迹象，且品系间凋亡相关蛋白免疫反应性未观察到显著差异。心肌TUNEL阳性细胞极为罕见，尽管在胸腺髓质和脾滤泡中存在凋亡。促凋亡蛋白Bax、Fas和FasL在所有组中均有表达，尽管与组织病理学无明显的明确相关性。相比之下，抗凋亡蛋白Bcl-2在对照中显示出轻度免疫反应性，感染后增加，且与两个品系的组织病理学评分密切相关。在两个品系的3周研究期内，心肌iNOS免疫反应性显示出与Bcl-2相似但较弱的染色模式。在心肌中未检测到ICE和p53免疫反应性。
因此，尽管有明显的炎症活动，但在CD1和C3H.HeJ小鼠的急性CVB3心肌炎中，心肌细胞凋亡很少见。
