CAJ | 학술논문

目的观察嗜铬粒蛋白A(chromogranin A,CGA)在扩张型心肌病(dilated cardiomyopathy,DCM)患者中的表达、心肌纤维化程度及二者间的关系,初步探讨CGA在心肌纤维化进程中的作用.方法取DCM心脏移植患者的心肌组织标本作为研究对象,排除心脏疾病的脑外伤尸检心肌组织标本作为对照.利用实时荧光定量聚合酶链反应(real-time PCR)检测心肌中CGA及Ⅰ型胶原纤维(COL Ⅰ)、Ⅲ型胶原纤维(COL Ⅲ)、ADAMTS-1的mRNA表达,并分析其基因学相关性.免疫组织化学技术鉴定心肌中CGA的分布位置及其表达强弱变化.运用苦味酸天狼猩红特异染色和偏振光显微镜显像,并辅以图像分析软件计算心肌胶原容积积分(CVF).并对CGA与心肌纤维化的相关性进行形态学上的比较.结果 real-time PCR证实心肌中CGA-mRNA和COL Ⅰ-mRNA、COLⅢ-mRNA、ADAMTS-1-mRNA三者均具有相关性,相关系数分别为0.729、0.95、0.665.免疫组织化学结果表明,DCM患者心肌中CGA表达增加(P<0.05).DCM患者心肌CVF高于正常心肌(P<0.001).形态学上,CGA呈现阳性的部位及其分布密集区域的附近,心肌纤维化明显.结论 DCM心肌中CGA的表达与心肌纤维化具有相关性,推测DCM患者心肌组织中CGA的表达水平影响着心肌纤维化的发展.
목적 관찰기락립단백A(chromogranin A,CGA)재확장형심기병(dilated cardiomyopathy,DCM)환자중적표체、심기섬유화정도급이자간적관계,초보탐토CGA재심기섬유화진정중적작용.방법 취DCM심장이식환자적심기조직표본작위연구대상,배제심장질병적뇌외상시검심기조직표본작위대조.이용실시형광정량취합매련반응(real-time PCR)검측심기중CGA급Ⅰ형효원섬유(COL Ⅰ)、Ⅲ형효원섬유(COL Ⅲ)、ADAMTS-1적mRNA표체,병분석기기인학상관성.면역조직화학기술감정심기중CGA적분포위치급기표체강약변화.운용고미산천랑성홍특이염색화편진광현미경현상,병보이도상분석연건계산심기효원용적적분(CVF).병대CGA여심기섬유화적상관성진행형태학상적비교.결과 real-time PCR증실심기중CGA-mRNA화COL Ⅰ-mRNA、COLⅢ-mRNA、ADAMTS-1-mRNA삼자균구유상관성,상관계수분별위0.729、0.95、0.665.면역조직화학결과표명,DCM환자심기중CGA표체증가(P<0.05).DCM환자심기CVF고우정상심기(P<0.001).형태학상,CGA정현양성적부위급기분포밀집구역적부근,심기섬유화명현.결론 DCM심기중CGA적표체여심기섬유화구유상관성,추측DCM환자심기조직중CGA적표체수평영향착심기섬유화적발전.
Objective To observe the possible correlation between expression of chormogranin A (CGA) and myocardial fibrosis and investigate the potential role of CGA in the development of myocardial fibrosis in patients with dilated cardiomyopathy ( DCM ). Methods Surgical myocardial specimen from 10 DCM patients underwent successful orthotopic cardiac transplantation, and 3 normal myocardial specimen from brain-dead organ donors were obtained. CGA-mRNA,COL I -mRNA, COL Ⅲ-mRNA and ADAMTS-1-mRNA were analyzed by real-time PCR. The location and expression of CGA were assessed by immunohistochemistry( INH) with anti-CGA antibody. The collagen specific picrosirus red staining was applied on transversal myocardial slides and the collagen volume fraction ( CVF) was calculated. The correlation between CGA and CVF was analyzed. Results Cytoplasic expression of CGA assessed by INH showed large amount of strong positive granules densely arranged in the epicardial and endocardial myocardiocytes in DCM specimen while there was only few sparse granules in the normal myocardium (P < 0.05). CVF was significantly higher in DCM myocardial specimen than that in normal specimen (P < 0. 001). CGA-mRNA was significantly correlated with COL I -mRNA (r = 0. 729), COL Ⅲ -mRNA (r = 0.95) and ADAMTS-1-mRNA (r =0.665, all P<0.05). Moreover, collagen deposition location was almost identical with the strong positive expression location of CGA. Conclusion We demonstrated for the first time that the deposition of CGA was related with the myocardial fibrosis in DCM heart, therefore, CGA might play an important role by influencing myocardial remodeling and fibrosis in DCM patients.