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Enteroviral Replication and Cardiocyte Injury in the Myocardium from patients with Dilated Cardiomyopathy and Perforin Knockout Mice with Viral Myocarditis

扩张型心肌病患者和穿孔素敲除病毒性心肌炎小鼠心肌中的肠道病毒复制和心肌细胞损伤

基本信息

批准号：
10670681
负责人：
DEGUCHI Hirofumi
金额：
$ 1.34万
依托单位：
Osaka Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

(1)Experimental Coxsackievirus B3 Myocarditis in Perforin Knockout (pfk) Mice.We examined light and (LM) electron-microscopic (EM) changes of the myocardium obtained from pfk and wild(C57BL/6) mice with Coxsackievirus B3(CVB3) myocarditis. The mice were sacrificed on days 5-28 after virus inoculation. On days 8 and 14 many cardiocytes underwent necrosis with infiltration of lymphocytes and macrophages. By immuno-EM perforin were often observed in the granules of lymphocytes. The lymphocytes were sometimes in close contact with plasma membrane of cardiocytes. In pfk mice, cardiocyte necrosis was less than in wild mice, although significant number of lymphocytes infiltrated in the myocardium. These findings suggest that perforin plays an important role in the development of lymphcyte-mediated cardiocyte injury.(2)Enteroviral RNA Replicatin in 26 Cases of Dilated Cardiomyopathy (DCM) with Refractory Heart FailureWe performed light microscopic in situ hybridization (ISH) and virological analyses of myocardial specimens obtained by partial left ventriculectomy. Myocardial specimens were tested for the presence and localization of enteroviral RNA in the myocardium by PCR and ISH. In PCR studies, both sense and antisense viral RNA were detected in the myocardium of seven patients(38%). The presence of these RNAs indicates active viral replication in the myocardium. On ISH, 3 patients had evidence of active replication of enteroviral genomes. Viral signals were found in degenerating cardiocytes, interstitial inflammatory cells and endothelial cells of small vessels. We detected both sense and antisense enteroviral RNA in various myhocardial lesions. Our results suggest that active viral replication plays a role in the development of myocardial lesions in DCM patients.

（1）穿孔蛋白基因敲除（Perforin Knockout，pfk）小鼠实验性柯萨奇B3病毒性心肌炎：观察了pfk和野生型（C57 BL/6）小鼠柯萨奇B3病毒性心肌炎的光镜和电镜改变。在病毒接种后第5-28天处死小鼠。在第8天和第14天，许多心肌细胞坏死，淋巴细胞和巨噬细胞浸润。免疫电镜观察，淋巴细胞颗粒内常可见穿孔素。淋巴细胞有时与心肌细胞质膜紧密接触。在pfk小鼠中，心肌细胞坏死比野生型小鼠少，尽管在心肌中有大量淋巴细胞浸润。这些结果表明，穿孔素在淋巴细胞介导的心肌细胞损伤的发展中起着重要作用。（2）26例扩张型心肌病（DCM）顽固性心力衰竭患者的肠道病毒RNA复制我们对左心室部分切除术后的心肌标本进行了光镜原位杂交（ISH）和病毒学分析。用PCR和ISH检测心肌标本中肠道病毒RNA的存在和定位。在PCR研究中，在7名患者（38%）的心肌中检测到正义和反义病毒RNA。这些RNA的存在表明心肌中病毒复制活跃。在ISH中，3例患者有肠道病毒基因组活跃复制的证据。在变性的心肌细胞、间质炎性细胞和小血管内皮细胞中发现病毒信号。我们检测到正义和反义肠道病毒RNA在各种心肌病变。我们的研究结果表明，活跃的病毒复制在DCM患者心肌病变的发展中起着重要作用。