THE ROLE OF HEPATITIS C VIRUS BY INDUCTION OF CARDIOMYOPATHY

丙型肝炎病毒诱发心肌病的作用

• 批准号: 13670547
• 负责人: SHIOMI Susumu
• 金额: $ 2.24万
• 依托单位: OSAKA CITY UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670547/
• 关键词: CARDIOMYOPATHY; HEPATITIS C VIRUS; TRANSGENIC MOUSE; HCV CORE PROTEIN; HCV ANTIBODY; HCV GENOTYPE; HCV-RNA; CARDIOMYOCYTE; AP-1; 肥大性心筋症; 培養心筋細胞; 肥大型心筋症; HCV-RNA

Hepatitis C virus (HCV) is the main cause of chronic hepatitis worldwide. HCV has been reported to be associated with cardiomyopathy. However, the mechanism of cardiomyopathy in chronic HCV infection is still unclear. The ability of the core protein of HCV to modulate gene transcription, cell growth and cell death may be involved in the pathogenesis of cardiomyopathy.Here, we report the development of cardiomyopathy in mice transgenic for the HCV core gene. After the age of 12 months, mice developed cardiomyopathy that appeared as left ventricular dilatation, and systolic and diastolic dysfunction. These cardiac changes were consisted with cardiomyocyte hypertrophy, myofiber disorganization, myofilament loss, myofiber disorganization, Z-band abnormalities, irregular shaped nuclei, increased number of mitochondria and aggregation of mitochondria.These results indicate that the HCV core protein has an important role in the development of cardiomyopathy, and that these transgenic mice provide good animal models for cardiomyopathy with HCV infection.

丙型肝炎病毒（HCV）是世界范围内慢性肝炎的主要病因。据报道，HCV与心肌病有关。然而，慢性HCV感染引起心肌病的机制尚不清楚。HCV核心蛋白对基因转录、细胞生长和细胞死亡的调节作用可能参与了心肌病的发病机制。12个月大后，小鼠出现心肌病，表现为左心室扩张，收缩和舒张功能障碍。这些心脏改变包括心肌细胞肥大、肌纤维结构紊乱、肌丝丢失、肌纤维结构紊乱、Z带异常、细胞核形状不规则、线粒体数目增多和聚集等，表明HCV核心蛋白在心肌病的发生发展中起重要作用，这些转基因小鼠为HCV感染的心肌病提供了良好的动物模型。

项目成果

Omura, et al.: "The core protein of hepatitis C virus induced cardiomyopathy in transgenic mice"J Med Virol. (In press).

Omura等人：“丙型肝炎病毒的核心蛋白在转基因小鼠中诱导心肌病”J Med Virol。

西口修平, 他: "循環器疾患におけるHCV抗体陽性率の検討-心筋症との比較"厚生科学研究費・非A非B型肝炎の臨床的総合研究・平成10〜12年度報告書. 160-161 (2002)

Shuhei Nishiguchi等人：“心血管疾病中HCV抗体阳性率的检查-与心肌病的比较”健康和福利科学研究资助/非甲非乙型肝炎的综合临床研究，1998-12报告。 (2002)

Teragaki M, et al.: "Prevalence of hepatitis C virus among patients with hypertrophic cardiomyopathy"Heart & Vessels. 18. 167-170 (2003)

Teragaki M 等人：“肥厚型心肌病患者中丙型肝炎病毒的患病率”心脏

西口修平, 他: "HCVトランスジェニックマウスにおける心筋症の検討"厚生科学研究費・新興・再感染症研究事業分担研究報告書・平成15年度報告書. (印刷中). (2004)

Shuhei Nishiguchi 等人：“HCV 转基因小鼠的心肌病检查”健康与福利科学研究资助/新发/再感染性疾病研究项目共享研究报告/2003 财年报告（2004 年）。

Omura T, Yoshiyama M, Hayashi T, Nishiguchi S, Fukuda K, Inamoto S, Nakamura y, Teragaki M, Iwao H, Takeuchi K, Yoshikawa J.: "The core protein of hepatitis C virus induced cardiomyopathy in transgenic mice"

Omura T、Yoshiyama M、Hayashi T、Nishiguchi S、Fukuda K、Inamoto S、Nakamura y、Teragaki M、Iwao H、Takeuchi K、Yoshikawa J.：“转基因小鼠丙型肝炎病毒诱发心肌病的核心蛋白”