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THE PATHOGENESIS OF LEFT VENTRICULAR STIFFNESSIN CARDIOMYOPATHIES : ULTRASTRUCTURAL AND IMMUNOHISTOCHEMICAL STUDY.

心肌病左心室僵硬的发病机制：超微结构和免疫组织化学研究。

基本信息

批准号：
07670819
负责人：
HAYASHI Tetsuya
金额：
$ 1.28万
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：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

To clarify the etiology of left ventricular stiffness in cardiomyopathies, the following studies were conducted. (1) On the right ventricular endomyocardial biopsy specimens, the subtypes of collage I,III and IV were analyzed ant the expression of MMP-1 and 2 werestudies semiquantitatively (graded from 0 to 3+) in 14 cases of restrictive cardiomyopathy (RCM), 21 of hypetrophic cardiomyopathy (HCM) and 23 of dilated cardiomyopathy (DCM) by immuno-light and electron microscopy. Furthermore, the MMP-2 activity measured by zymography in 7 KCM 10 DCM cases were comparted with the normal control (n=5) obtained at the bypass surgery. Immunohistochemically, type III collagenincreased remarkably in RCM and HCM,whereas type I and IV collagen was prominent in DCM.The immunoreactivity ageinst MMP-1 was positive along collagen fibrils and in some fibroblasts both in HCM and DCM.The MMP-1 tended to increase as the reactivity against type I and III collagen was prominent. On the other hand, the MMP-2 … More and its activity measured by zymography were prominent in DCM.(2) To elucidate the three dimensional architecture of cardiocytes, collagen and elastic fibers, fifteen autopsied hearts (4 RCM,1obstructuve HCM,3 DCM,2 myocardial infarction, OMI and 5 normal hearts without cardiacdisease) and 3 surgical materials (2 obstructive HCM and 1OMI) were studied by scanning electron microscopy. In RCM and HCM,the cardiocytes were bizarrely shaped and branching, and were irregularly connected with one another. The most striking features in RCM was the thickened perimysium in which collagen bundles of less than 5 mum formed reticular networks together with an increased amount of elastic fibers, which were very similar to those in HCM.On the other hand, in DCM and OMI,endomysium and perimysium were both thickened but the elastic fibers was small in amount. Furthermore, in the perimysium of DCM and OMI,collagens were often organized into thick bundles up 20 mum which ran along the longitudinal axis of neighboring cardiocytes. The above findings suggest that 1) increased reticular networks, which were supposed to be type III colllagen, and elastic elements play an important role as the cause of left ventricular stiffness in RCM and HCM,2) the increased collagen type I reflects the replacement fibrosis in DCM,and 3) MMP appeared to be involved in a cascade of collagen synthesis and the remodeling of the heart in cardiomyopathies. Less

为了阐明心肌病左室僵硬的病因，进行了以下研究。(1)对右室心内膜心肌活检标本进行I、III、IV型胶原亚型分析，并对14例限制性心肌病(RCM)、21例肥厚型心肌病(HCM)、23例扩张型心肌病(DCM)患者的心肌组织进行免疫组织化学染色，半定量(0~3+)检测基质金属蛋白酶1和2的表达。此外，对7例KCM和10例DCM患者进行了酶谱检测，并与5例正常对照(n=5)进行了比较。免疫组织化学显示，RCM和HCM中III型胶原明显增多，而DCM中以I型和IV型胶原为主。基质金属蛋白酶-1在胶原纤维和部分成纤维细胞中均呈阳性反应，且随着对I型和III型胶原反应的增强而增加。另一方面，基质金属蛋白酶-2…(2)对15例尸检心脏(4例RCM、1例梗阻心肌、3例DCM、2例心肌梗死、OMI和5例无心脏病的正常心脏)和3例手术材料(2例梗阻性心肌梗死、1例梗阻性肥厚型心肌梗死和1例非梗阻性肥厚型心肌梗死)和3例外科手术材料(梗阻性肥厚型心肌和10例肥厚型心肌梗死)进行了扫描电子显微镜观察。RCM组和HCM组心肌细胞形态和分支形态异常，彼此间连接不规则。RCM最显著的特征是肌束膜增厚，5微米以下的胶原束形成网状网络，弹性纤维增多，与CM相似。DCM和OMI的肌内膜和肌周均增厚，但弹性纤维数量较少。此外，在扩张型心肌病和陈旧性心肌梗塞的肌束膜上，胶原通常排列成厚束状，长达20微米，沿相邻心肌细胞的纵轴排列。上述结果提示：1)RCM和HCM患者左心室僵硬的重要原因是网状结构和弹性元件的增多，I型胶原的增加反映了DCM的替代纤维化；3)在心肌病中，基质金属蛋白酶参与了胶原合成和心脏重塑的级联反应。较少