Ilbäck N G, Lindh U, Wesslén L, Fohlman J, Friman G
Toxicology Division, National Food Administration, Uppsala, Sweden.
Biol Trace Elem Res. 2000 Winter;78(1-3):131-47. doi: 10.1385/BTER:78:1-3:131.
Methyl mercury (MeHg) has been shown to change Coxsackie virus type B3 (CB3) myocarditis in a direction compatible with the development of chronic disease. Murine models of CB3 myocarditis closely mimic the pathogenesis in humans. There are also indications that metals, such as mercury, and trace elements may interact and adversely affect viral replication and development of inflammatory lesions. The effects of low-dose MeHg exposure on myocardial trace element distribution, as determined by means of nuclear microscopy, was studied in CB3 myocarditis. Balb/c mice were fed a MeHg-containing diet (3.9 mg/kg diet) for 12 wk prior to infection. Areas of inflammatory lesions in the myocardium were identified by traditional histologic examination, and serial tissue sections in these selected areas were used for immune histology (macrophages), in situ hybridization of virus genomes, and nuclear microscopy of tissue trace element distribution. Areas with no inflammation or virus were compared with areas of ongoing inflammation and viral replication. In the inflammatory lesions of MeHg-exposed mice as compared to nonexposed mice, the myocardial contents of calcium (Ca), manganese (Mn), and iron (Fe) were significantly increased, whereas the zinc (Zn) content was decreased. The increased Ca and decreased Zn contents in the inflamed heart may partly explain a more severe disease in MeHg-exposed individuals. Although not significant in the present study, with a limited number of mice, the inflammatory and necrotic lesions in the ventricular myocardium on d 7 of the infection was increased by 50% (from 2.2% to 3.3% of the tissue section area) in MeHg-exposed mice and, also, there was a tendency of increased persistence of virus with MeHg exposure. No increased MeHg uptake, either in the inflammatory lesions or in the areas of noninflamed heart tissue in infected mice, could be detected. The present results indicate that a "competition" exists between potentially toxic heavy metals from the environment/diet and important trace elements in the body and that a disturbed trace element balance adversely influences the development of pathophysiologic changes in inflammatory heart disease.
甲基汞（MeHg）已被证明会使B3型柯萨奇病毒（CB3）心肌炎朝着与慢性病发展相一致的方向转变。CB3心肌炎的小鼠模型与人类发病机制极为相似。也有迹象表明，汞等金属和微量元素可能相互作用，并对病毒复制和炎性病变的发展产生不利影响。本研究采用核显微镜技术，研究了低剂量甲基汞暴露对CB3心肌炎心肌微量元素分布的影响。在感染前，给Balb/c小鼠喂食含甲基汞的饲料（3.9毫克/千克饲料），持续12周。通过传统组织学检查确定心肌中的炎性病变区域，并将这些选定区域的连续组织切片用于免疫组织学（巨噬细胞）、病毒基因组原位杂交以及组织微量元素分布的核显微镜检查。将无炎症或无病毒的区域与正在发生炎症和病毒复制的区域进行比较。与未暴露小鼠相比,暴露于甲基汞的小鼠的炎性病变中，心肌中的钙（Ca）、锰（Mn）和铁（Fe）含量显著增加，而锌（Zn）含量降低。发炎心脏中钙含量增加和锌含量降低可能部分解释了甲基汞暴露个体中病情更严重的原因。虽然在本研究中不显著，且小鼠数量有限，但在感染第7天时，暴露于甲基汞的小鼠心室心肌中的炎性和坏死病变增加了50%（从组织切片面积的2.2%增至3.3%），而且，甲基汞暴露还有使病毒持续存在时间增加的趋势。在感染小鼠的炎性病变或未发炎心脏组织区域中，均未检测到甲基汞摄取增加。目前的结果表明，来自环境/饮食的潜在有毒重金属与体内重要微量元素之间存在“竞争”，并且微量元素平衡紊乱会对炎性心脏病病理生理变化的发展产生不利影响。
