【作者】 张近宝；

【导师】 刘维永；

【作者基本信息】 第四军医大学 ， 外科学， 1999， 博士

【摘要】 目的：拟通过慢性风湿性和创伤性二尖瓣关闭不全所致慢性心肌病变及相关细胞因子的变化比较，在蛋白质及基因水平等不同层次揭示慢性风湿性和创伤性二尖瓣关闭不全的病理机制，并与临床资料对比，以期了解心肌纤维化和心功能关系和探讨心肌纤维化血清学诊断指标。 方法：取临床风心病二尖瓣关闭不全换瓣切下的左室乳头肌标本，并与创伤性二尖瓣关闭不全模型犬的左室乳头肌标本对照，分别行HE、Masson染色，免疫组化和原位杂交，以检测两种不同致病因素所致心肌病理及相关细胞因子变化，研究其关系，并与临床患者血清中前胶原的含量进行相关性分析。 结果：①慢性风湿性二尖瓣关闭不全心肌间质明显增生，其纤维化程度约为正常的3.28～3.72倍；血管内膜增生，管壁增厚，管腔狭窄；Ⅰ、Ⅲ型胶原和前胶原mRNA除在间质细胞中呈明显阳性表达外，病变心肌细胞中也出现阳性表达，提示心肌细胞参与了间质纤维化。创伤性二尖瓣关闭不全心肌病变，早期(伤后3个月)是间质胶原正常或减少，血管密度增加，心肌重量比正常增加13％，心肌呈离心性肥厚，免疫组化检测心肌细胞中Ⅰ、Ⅲ型胶原表达为阴性。后期(伤后5～7个月)亦有间质胶原增生，约比正常增生20％，间质血管更多还原

【Abstract】 Objective: In order to reveal mechanism of rheumatic mitral regurgitation and trauma mitral regurgitation in protein and gene level, we studity myocardial pathology of RMR and TMR which caused chronic myocardium changes and related cytokine changes, and compared with clinical information to explor the relationship between myocardial fibrosis and heart function , and to find the criterion of myocardial fibrosis with serodiagnosis..Methods: Left ventricle papillary muscles were obtained from rheumatic heart disease during mitral valve replacement and also from canine traumatic mitral regurgitation model. The specimens were stained by HE stain, Masson stain, im-munhistochemical stain and in situ hybridization to examine myocardium pathology and related cytokine changes caused by two different nosogenesis, and to be correlating analyzed with procollagen concentration in clinical patients serum.Results: ①Myocardium interstitium hyperplasia markedly in RMR myocardium and the degree of fibrosis was as 3.28～3.72 times as normally. Vessel endothe-liosis and vascular wall thickness with lumen stenosis also appeared. The positive expression of type I and type I collagen and procollagen mRNA either appeared in interstitium cells or in myocardium cells. It suggested that cardiomy-ocyte also involved interstitium fibrosis. In the early phase of TMR collagen in myocardiac was normal or decreased and the vascular density inereased. My-更多还原