缺血性心肌病胶原代谢标志物的改变及其临床意义

Change in the collagen metabolic markers of ischemic cardiomyopathy and its clinical significance

目的探讨金属蛋白酶(MMP)及其内源性抑制物(TIMP)对缺血性心肌病患者(ICM)心室重构的调控作用以及与心脏功能的关系,同时观察ACEI类药物的干预作用。方法对2003年1月至2006年1月武汉大学人民医院86例ICM患者及25例正常对照者采用ELISA和放射免疫法测定MMP-9、TIMP-1及胶原代谢产物PICP和ICTP的血浆浓度。对照组和卡托普利组治疗24周前后分别测定上述指标和相关超声心动图参数。结果ICM组MMP-9、TIMP-1及MMP-9/TIMP-1质量浓度均较正常对照组显著增高(P均<0.01)。ICTP在ICM组质量浓度明显高于对照组[(4.5±0.8)μg/L对(2.4±0.7)μg/L],P<0.05。PICP/ICTP比值与TIMP-1呈正相关(r=0.673,P=0.0286),且与MMP-9呈负相关(r=-0.458,P=0.0272)。24周后,卡托普利组的MMP-9、TIMP-1及其比值均明显下调(P<0.05),ICTP明显降低(P<0.05),而PICP/ICTP则明显升高(P<0.05)。E/A和LVEF均与MMP-9/TIMP-1呈相关关系(r=0.712,P=0.018及r=-0.67,P=0.036)。结论ICM患者血浆中心肌胶原代谢的生化标志物升高,胶原降解活跃,且与心脏功能参数相关,ACEI药物可一定程度抑制其异常代谢,提示这些标志物尤其是MMP-9/TIMP-1,是无创评价ICM患者心室重构、心肌纤维化以及病程发展的良好指标之一。

To investigate the pathological contribution of serological markers of collagen metabolism inclu-ding matrix-metalloproteinases（MMPs） and its tissue inhibitors（TIMPs） ,the markers for type I collagen degradation（ IC-TP） and synthesis（PICP） to cardiac remodeling of ischemic cardiomyopathy（ ICM ）as well as the pharmacological regula-tion effect. Methods Plasma levels of MMP-9,TIMP-1,ICTP and PICP were determined by ELISA and RIA in 86 con-secutive ICM patients and 25 age-matched control subjects, Patients were divided into two subgroups according to ACEI-taking or not, Echocardiography were performed in all cases, Results The plasma concentration of MMP-9,TIMP-1 and MMP-9/TIMP-1 was significantly increased in ICM group（ all P 〈0.01） as well as ICTP（ P〈0.05）, PICP/ICTP ratio in ICM group was significantly lower than controls （ P〈0.05）, After 24 weeks of follow-up, all the above parameters were improved （ P 〈 0.05）, PICP/ICTP ratio correlated positively with TIMP-1（ r=0.673, P=0.0286） , negatively with MMP-9（r=-0.458,P=0.0272）. E/Aand LVEFcorrelated with MMP-9/TIMP-1（r=0.712,P=0.018 及 r=-0.67, P=0.036）. Conclusion Biomarkers of collagen degradation are elevated, and correlat with heart function; MMP-9/ TIMP-1 serves as a valuable index for fibrosis and progression of cardiac dilation in ICM patients ;ACEI can partially re-verse the disregulation of collagen metabolism.