【作者】 荆志成；

【导师】 程显声； 杨英珍；

【作者基本信息】 中国协和医科大学 ， 内科学， 1998， 博士

【摘要】 在我国，病毒性心肌炎(viral myocarditis，VMC)的发病逐年增多。随着风湿性等心肌炎的减少，临床大部分心肌炎实际是病毒性的，成为严重危害人民，尤其是小儿和青年人健康的常见病。临床发现，大部分进入慢性期的VMC患者常见有心脏舒张功能不全，如何解释这种现象，成为临床医师所关注的问题。 近年来的研究表明，心脏间质，尤其是Ⅰ型、Ⅲ型胶原的病理表达是心功能障碍的一个重要原因。资料证实VMC慢性期主要病理特点是心脏间质纤维化，用现代观点解释，即心脏胶原网络(Cardiac collagen network，CCN)增生性重建，这可能与VMC心脏舒张功能不全有关。但关于这方面的研究，国内外均未见到报道。本文旨在通过建立柯萨奇B3(CVB3)VMC小鼠模型，观察：①VMC小鼠急性期到慢性期心脏胶原表达变化及其与心脏功能变化间的关系；②血管紧张素Ⅱ(AⅡ)受体拮抗剂losartan干预后，各期VMC小鼠心脏胶原表达与心脏功能的变化；③各期VMC小鼠血浆AII和醛固酮(ALD)浓度变化及其与心脏胶原表达变化间的关系；④CVB3mRNA在各期VMC小鼠心肌中的表达。 总之，本文试图阐明心肌纤维化在VMC发生、发展中的作用，及其与心脏功能变化间的关系，探讨心肌纤维化的机制及药物干预的效果。 方法 1．动物及实验分组更多还原

【Abstract】 The cases clinically diagnosed as viral myocarditis have been increasing recent years in China. Instead of rheumatic myocarditis, viral myocarditis has become the most common myocarditis which seriously threaten human health, especially in adolescents and children. A feature of viral myocarditis is the cardiac diastolic dysfunction at the chronic stage. However, the molecular mechanism for this remains unclear. Recent studies suggested that pathologic expression of myocardial interstitium, particularly type I and III collagen may be an important reason for cardiac dysfunction. And some literatures suppose that the proliferative remodeling of cardiac interstitial collagen network during viral myocarditis is responsibe for cardiac diastolic dysfunction.But there is no experimental evidence to support the hypothesis so far. In order to illustrate the role of myocardial fibrosis in the pathogenesis and development of VMC, and its relationship to the cardiac function alteration, Coxsackievirus B3 myocarditis models were established, and using the models, the following studies have been done:(1) the myocardial collagen expression and its relation to the cardiac function in the VMC mice from the acute stage to chronic stage;(2)the changes in myocardial collagen expression and the cardiac function in the VMC mice at each stage intervened with losartan,an AII receptor antagonist;(3)the relationship更多还原