Impaired expression of cardiac adiponectin in leptin-deficient mice with viral myocarditis.
Impaired expression of cardiac adiponectin in leptin-deficient mice with viral myocarditis.
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DOI：
10.1536/ihj.47.107
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发表时间：
2006
影响因子：
1.5
通讯作者：
Takashi Takahashi;F. Yu;S. Saegusa;H. Sumino;T. Nakahashi;K. Iwai;S. Morimoto;M. Kurabayashi;T. Kanda
中科院分区：
文献类型：
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作者：
Takashi Takahashi;F. Yu;S. Saegusa;H. Sumino;T. Nakahashi;K. Iwai;S. Morimoto;M. Kurabayashi;T. Kanda
采用脑心肌炎（EMC）病毒诱导的小鼠心肌炎模型，研究脂联素在受损心肌细胞中的表达。我们将EMC病毒腹腔注射到瘦素缺陷型ob/ob（OB）小鼠和野生型（WT）小鼠中。将OB小鼠分为两个亚组，由无干预的小鼠和接受与病毒接种同时开始的瘦素替代的小鼠组成。我们确定了OB小鼠和WT小鼠之间的心脏重量、心脏组织学评分、心肌中浸润和凋亡细胞的数量、心脏中脂联素和TNF-α mRNA的表达水平、肌细胞中脂联素的免疫反应性、心脏中脂联素和TNF-α的浓度以及肌细胞中脂联素受体的免疫反应性的差异。与WT小鼠相比，在病毒接种后第4天和第8天，OB小鼠心脏中脂联素mRNA表达、免疫反应性和蛋白水平显著降低，心肌细胞中脂联素受体1的免疫反应性降低，同时心脏重量增加，严重的炎症性心肌损伤，心脏TNF-α mRNA和蛋白水平升高。在OB小鼠中替代瘦素通过增加脂联素mRNA、免疫反应性和蛋白水平、增加肌细胞中脂联素受体1免疫反应性和抑制TNF-α mRNA和蛋白水平来抑制严重心肌炎的发展。这些结果表明，心肌脂联素的表达受损可能有助于通过增强表达的TNF-α在瘦素缺乏条件下的病毒性心肌炎的进展。
A mouse model of encephalomyocarditis (EMC) virus-induced myocarditis was used to investigate the expression of adiponectin in damaged cardiomyocytes. We intraperitoneally injected EMC virus into leptin-deficient ob/ob (OB) mice and wild-type (WT) mice. OB mice were divided into two subgroups consisting of mice with no intervention and mice receiving leptin replacement starting simultaneously with viral inoculation. We determined differences in heart weight, cardiac histological score, numbers of infiltrating and apoptotic cells in the myocardium, expression levels of adiponectin and TNF-alpha mRNA in the heart, adiponectin immunoreactivity in myocytes, adiponectin and TNF-alpha concentrations in the heart, and immunoreactivity of adiponectin receptors in myocytes between OB mice and WT mice. There was significantly decreased adiponectin mRNA expression, immunoreactivity, and protein level in the heart, and reduced immunoreactivity of adiponectin receptor 1 in myocytes from OB mice on days 4 and 8 after viral inoculation as compared with those in WT mice, together with increased cardiac weight, severe inflammatory myocardial damage, and increased levels of cardiac TNF-alpha mRNA and protein. Replacement of leptin in OB mice inhibited the development of severe myocarditis through augmentation of adiponectin mRNA, immunoreactivity, and protein level, increased adiponectin receptor 1 immunoreactivity in myocytes, and suppressed levels of TNF-alpha mRNA and protein. These results suggest that impaired expression of cardiac adiponectin may contribute to the progression of viral myocarditis through enhanced expression of TNF-alpha under a leptin-deficient condition.