CTGF和MT1-MMP在容量超负荷导致心室间质重塑中的表达

Expression of CTGF and MT1-MMP in extracellular matrix remodeling of left ventricle induccd by volume overload

目的探讨结缔组织生长因子(CTGF)和1类膜型基质金属蛋白酶(MT1-MMP)在主动脉瓣关闭不全产生容量超负荷导致心室间质重塑中的表达及作用。方法29例手术患者,分为容量超负荷组(VO)13例,以主动脉瓣关闭不全为主的双瓣病变患者,主动脉瓣跨瓣压差小于或等于20mmHg,瓣膜反流面积大于或等于6.0cm2;二尖瓣狭窄组(MS)16例,为单纯二尖瓣狭窄进行单瓣置换术患者;对照组为5例意外死亡成年健康人,标本在死亡30min内取得。采用心脏彩超分析术前患者心功能状况;术中取患者左室乳头肌同对照组心肌一起做心肌胶原纤维Masson染色,测定心肌胶原纤维含量;运用RT-PCR技术对各例标本CTGF mRNA和MT1-MMP mRNA表达情况进行分析。结果VO组患者由于容量超负荷,形成离心性肥厚,MS组心肌肥厚不明显。VO组患者心肌胶原纤维增生较MS组及对照组增生相当明显,血管壁增厚,管腔变窄,腔外胶原纤维增生,差异有统计学意义(P<0.05)。VO组CTGF mRNA、MT1-MMP mRNA表达量均明显高于MS组和对照组(P<0.01);MS组与对照组CTGF mRNA、MT1-MMP mRNA表达量均明显偏低,MS组CTGF mRNA表达略高于对照组(P<0.05);MS组与对照组MT1-MMP mRNA表达差异无统计学意义(P>0.05)。结论CTGF与MT1-MMP在主动脉瓣关闭不全导致容量超负荷情况下的表达增强,可能参与了心肌离心性肥厚及心室间质重塑的发展过程。

Objective To approach the expression of CTGF and MT1-MMP in valve disease with volume overload which induces extracellular matrix remodeling of left ventricle. Methods Of 29 patients,13 cases were volume overload group（VO） ,which were the multiple valve disease with predominately aortic insufficiency,cross valve pressure gradient equal or less than 20mm Hg, and valvular regurgitation more than 6.0cm2 ;16 cases were mitral stenosis group（MS）, which composed of simple mitral stenosis patients with single valve replacement. Meanwhile, 5 normal persons were the control group, which died from accidental. Echocardiography was used to analyze the left ventricular function and detect the hypertrophic level of the left ventricule. Meanwhile,left ventricle muscle samples were obtained during operation. Histological features were studied by using Masson staining,and collagenous contents were quantitated with a computer-assisted imaging analysis system. The expression of CTGF mRNA and MT1-MMP mRNA were detected with RT-PCR methods. Results In VO group, the eccentric hypertrophy was significantly,and myocardial hypertrophy was not found in MS group. Compared witn the MS group and control group, collagenous contents of left ventricle were significantly hyperplasia, vessel wall became thickening, and lumen of blood vessel got narrowing in VO group（P〈0.05）. Compared with MS group and control group,the mean level of CTGF mRNA and MT1-MMP mRNA expression were significantly increased in VO group（P〈0.01）. The mean levels of CTGF mRNA and MT1-MMP mRNA expression in MS and control group were both lower. There were no statistical difference of MT1-MMP mRNA expression between MS group and control group（P〉0.05）, but CTGF mRNA expression was increased in MS group compared with control group（P〈0.05）. Conclusion Expression of CTGF mRNA and MT1-MMP mRNA significantly increase in volume overload induced by aortic rgurgitation. It may be one of the important factors which takes participate in the progress of eccentric hypertrophy and the process of extracellular matrix remodeling of left ventricle.