结缔组织生长因子和Ⅰ类膜型基质金属蛋白酶在主动脉瓣狭窄患者心室间质重塑中的表达及作用

Expressions and roles of CTGF and MT1-MMP in extracellular matrix remodeling of left ventricle in patients with aorta valve stenosis

目的探讨结缔组织生长因子(connective tissue growth factor,CTGF)和Ⅰ类膜型基质金属蛋白酶(membrane type 1 matrix metalloproteinases,MT1-MMP)在瓣膜疾病所产生压力超负荷导致心室间质重塑中的表达及作用。方法32例手术患者分为2组:压力超负荷组(PO)16例,以主动脉瓣狭窄为主的双瓣病变,主动脉瓣口径长≤1.3cm,跨瓣压差≥40mmHg,瓣膜反流不超过4.0cm2;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例意外死亡成年正常人,标本在死亡0.5h内取得。采用心脏彩超分析术前患者心功能状况;术中取患者左心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、MT1-MMP mRNA表达情况进行分析。结果PO组患者由于左心室压力超负荷,形成向心性肥厚,MS组心肌肥厚不明显。PO组患者心肌胶原纤维较MS组及对照组增生明显,血管壁增厚,管腔变窄,腔外胶原纤维增生(P<0.01)。PO组CTGF、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、MT1-MMP mRNA表达量均明显偏低,MS组CTGF mRNA表达高于对照组(P<0.05);MS组与对照组MT1-MMP mRNA表达差异不明显(P>0.05)。结论CTGF与MT1-MMP在压力超负荷情况下的表达增强,可能参与了心肌向心性肥厚的发展过程。

Objective To approach the expressions and the roles of connective tissue growth factor （CTGF） and membrane type 1 matrix metalloproteinases （MT1-MMP） in valve disease with pressure overload which induces extraeellular matrix remodeling of left ventricle. Methods Of 32 patients, 16 cases were pres- sure overload group （PO）, who had the multiple valve disease with predominately aortic valve stenosis, having a ring diameter of aorta valve less than 1.3 era, cross valve pressure gradient equal or more than 40 mmHg, and valvular regurgitation less than 4.0 cm2; The other 16 cases, as mitral stenosis group （MS）, were simple mitral stenosis patients with single valve replacement. Meanwhile, 5 normal individuals served as control, who died from accident. Eehoeardiography was used to analyze the left ventricular function and detect the hypertrophic level of the left ventricle. Left ventricle muscle samples were obtained during operation. Histological features were studied by Masson staining, and eollagenous contents were quantitated with a computer-assisted imaging analysis system. The mRNA expressions of CTGF and MTI-MMP were detected with RT-PCR. Results Concentric hypertrophy was observed significant in PO group, but myocardial hypertrophy was not found in MS group. Compare to the MS group and control, PC） group had significantly more collagenous contents in left ventricle, thickened vessel wall, and narrow lumen of blood vessel （P 〈 0. 05 ）. The mean mRNA levels of CTGF and MT1-MMP were significantly increased in PC） group than in MS group and control （P 〈 0. 01 ）. The mRNA levels of CTGF and MTI-MMP expressions in MS and control group were both lower. There was no statistically difference of MT1-MMP mRNA expression between MS group and control group （ P 〉 0.05 ） , but CTGF mRNA expression was increased in MS group compare to control （P 〈 0.01 ）. Conclusion CTGF and MT1-MMP expressions are significantly increased at mRNA level in pressure overload induced by valve dis- ease. It may be one of the important factors which is involved in the progress of concentric hypertrophy and the process of extracellular matrix remodeling of left ventricle.