A study on the mechanism of myocardial injury in myocarditis and dilated cardiomyopathy.

心肌炎和扩张型心肌病心肌损伤机制的研究。

• 批准号: 11670714
• 负责人: NISHIKAWA Toshio
• 金额: $ 1.54万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670714/
• 关键词: Dilated cardiomyopathy; chronic myocarditis; rat; tissue injury; infiltrated lymphocyte; apoptosis; Fas; Fas ligand system; 抗Fas抗体; 抗Fas ligand抗体; 病理組織学; Fas-Fas ligand; Fas-Fas ligand抗体投与; Apoptosis; 病因; 脾臓; メモリーT細胞

It has generally been recognized that myocarditis may be implicated in the pathogenesis of dilated cardiomyopathy. However, the mechanism of myocardial damage in the chronic stage of myocarditis is still unclear. In this study myocarditis was induced in Lewis rats by injection of porcine cardiac myosin and rats were harvested on day 21 or 74 after the initial injection. Apoptotic cell death was confirmed by in situ nick end labeling assay and gel-electrophoresis for DNA fragmentation on day 21, but none was disclosed on day 74. The expression of Fas mRNA and protein was detected on day 21 in the myocardium. In addition, Fas ligand was detected in some infiltrating lymphocytes. Some rats were injected with anti-Fas antibody or anti-Fas ligand antibody, and subsequently, myocardial damage was less severe than that in untreated rats on day 74. These results suggested that inhibition of apoptotic phenomenon in the acute stage may be related to the reduction of myocardial damage in the chronic stage of myocarditis.

人们普遍认为心肌炎可能与扩张型心肌病的发病机制有关。然而，心肌炎慢性期心肌损害的机制尚不清楚。本研究采用猪心肌肌球蛋白注射诱导Lewis大鼠心肌炎模型，分别于注射后第21天或74天取材。原位缺口末端标记法和DNA凝胶电泳法在第21天证实细胞死亡，但在第74天未发现细胞死亡。第21天检测到心肌Fas基因和蛋白的表达。此外，在一些浸润性淋巴细胞中还检测到Fas配体。部分大鼠注射抗Fas抗体或抗Fas配体抗体，74d时心肌损伤程度轻于未治疗组。提示心肌炎急性期抑制细胞凋亡现象可能与其减轻慢性期心肌损伤有关。

项目成果

Takashi Shimjo: "Nitric oxide induces apoptotic death of cardiomyocytes via a cyclic-GMP-dependent pathway"Exp Cell Res. 247. 38-47 (1999)

Takashi Shimjo：“一氧化氮通过环 GMP 依赖性途径诱导心肌细胞凋亡”Exp Cell Res。

Toshio Nishikawa: "Programmed cell death in the myocardium of arrhythmogenic right ventricular cardiomyopathy in children and adults"Cardiovasc Pathol. 8. 185-189 (1999)

Toshio Nishikawa：“儿童和成人致心律失常性右心室心肌病心肌中的程序性细胞死亡”心血管病理。

Toshio Nishikawa: "The role of superoxide and nitric oxide in the development of myocardial injury in rat myocarditis."Microscopy Microanalysis. 6(suppl 2). 488-489 (2000)

Toshio Nishikawa：“超氧化物和一氧化氮在大鼠心肌炎心肌损伤发展中的作用。”显微镜微分析。

Jun-ichi Suzuki: "Antisense bcl-x oligonucleotide induces apoptosis and prevents arterial neointimal formation in murine cardiac allografts."Cardiovascular Research. 45. 783-787 (2000)

Jun-ichi Suzuki：“反义 bcl-x 寡核苷酸诱导细胞凋亡并防止小鼠心脏同种异体移植物中动脉新内膜形成。”心血管研究。

Toshio Nishikawa: "Histopathologic aspects of endomyocardial biopsy in pediatric patients with idiopathic ventricular tachycardia"Pediatrics Int. 41. 534-537 (1999)

Toshio Nishikawa：“特发性室性心动过速儿科患者心内膜心肌活检的组织病理学方面”Pediatrics Int。