慢性心力衰竭患者外周血 MMP—2 、 MMP—9 、 TIMP—1 水平及其与预后的关系

摘要

目的:检测慢性心力衰竭(CHF)患者外周血基质金属蛋白酶(MMP)—2 、 MMP—9 、基质金属蛋白酶组织抑制剂(TIMP)—1水平,分析它们与CHF预后的关系.方法:选择2015年3月～2017年3月在本院住院的CHF患者200例为CHF组;根据NYHA心功能分级,被进一步分为 II级组(78例) 、 III级组(68例)和 IV级组(54例) ;根据预后情况, CHF组被分为预后良好组(126例)和预后不良组(74组) .选择同期健康体检者150例作为健康对照组.测量比较各组外周血血清MMP—2 、 MMP—9 、 TIMP—1水平.结果:与健康对照组比较, CHF组患者外周血血清MMP—2 、 MMP—9水平显著升高,TIMP—1水平显著降低, P均＝0.001 .随着NYHA心功能分级的升高,外周血清MMP—2 、 MMP—9水平逐渐升高, TIMP—1水平逐渐降低,两两比较均有显著差异, P均＝0.001 .与预后良好组比较,预后不良组外周血清 MMP—2 [ (47. 72 ± 9.57 ) ng／ml比(57. 42 ± 8. 63 ) ng／ml] 、MMP—9 [ (50.63 ± 8.95) ng／ml比(62.83 ± 9. 67) ng／ml]水平显著升高, TIMP—1水平[ (29.68 ± 6.43) ng／ml比(20.74 ± 4.07) ng／ml]显著降低, P均＝ 0.001 . MMP—2 、 MMP—9和 TIMP—1判断不良预后的 AUC分别为0.689 、 0. 683和0. 871 ; MMP—2≥51.13ng／ml 、 MMP—9≥57.67ng／ml 、 TIMP—1＜24.79ng／ml预测CHF患者不良预后的敏感性和特异性分别为 59.12% 和 80.93%、 67. 57% 和73.86%、 94.19% 和 81.79%,约登指数分别为0.616 、 0. 623和0. 516 . Kaplan—Meier分析法显示:按 2 年不良预后率, MMP—2 高水平者显著高于低水平者(78.05% 比8.47%) , MMP—9高水平者显著高于低水平者(72. 09% 比10.53%) , TIMP—1低水平者显著高于高水平者(87. 18% 比4.92%) , P均＝0. 001 .结论: MMP—2 、 MMP—9水平在CHF患者外周血中显著升高, TIMP—1水平显著降低,显著影响患者预后,可能为CHF患者预后的有效标志物.%Objective :To detect peripheral serum levels of matrix metalloproteinase (MMP)—2 ,MMP—9 and tissue in—hibitor of metalloproteinases (TIMP)—1 in CHF patients ,and analyse their relationship with CHF prognosis .Meth—ods : A total of 200 CHF patients ,who were hospitalized in our hospital from Mar 2015 to Mar 2017 ,were enrolled as CHF group ;according to NYHA classification ,they was further divided into class II group (n＝ 78 ) ,class III group (n＝68) and class IV group (n＝ 54 ) ;according to prognostic condition ,CHF group was divided into good prognosis group (n＝126) and poor prognosis group (n＝74).Another 150 healthy subjects were enrolled as healthy control group .Peripheral serum levels of MMP—2 ,MMP—9 and TIMP—1 were measured and compared among all group .Results : Compared with healthy control group , there were significant rise in peripheral serum levels of MMP—2 and MMP—9 ,and significant reduction in TIMP—1 level in CHF group , P＝ 0.001 all.Along with NYHA class rose , peripheral serum levels of MMP—2 and MMP—9 gradually increased , and TIMP—1 level gradually de—creased ,there existed significant difference between any two subgroups , P＝0.001 all.Compared with good prog—nosis group ,there were significant rise in peripheral serum levels of MMP—2 [ (47.72 ± 9.57) ng／ml vs.(57. 42 ± 8.63) ng／ml] ,MMP—9 [ (50. 63 ± 8. 95) ng／ml vs.(62.83 ± 9. 67) ng／ml] ,and significant reduction in TIMP—1 level [ (29. 68 ± 6. 43) ng／ml vs.(20.74 ± 4.07) ng／ml] , P＝0.001 all.AUCs of MMP—2 ,MMP—9 and TIMP—1 judging poor prognosis was 0.689 ,0.683 and 0. 871 respectively ;sensitivity and specificity of MMP—2≥51. 13ng／ml , MMP—9≥57. 67ng／ml ,TIMP—1＜24. 79ng／ml predicting poor prognosis in CHF patients were 59.12% and 80. 93%, 67. 57% and 73.86%,94.19% and 81.79% respectively ,and their Youden＇s indexes were 0. 616 ,0.623 and 0. 516 respectively .Kaplan—Meier analysis indicated that according to two—year poor prognosis rate ,the high level MMP—2 patients was significantly higher than that of low level patients (78.05% vs.8.47%) ,and that of high level MMP—9 patients was significantly higher than that of low level patients (72.09% vs.10.53%) ,and that of low level TIMP—1 patients was significantly higher than that of high level patients (87.18% vs.4.92%) , P＝0.001 all.Con—clusion : There are significant rise in MMP—2 and MMP—9 levels ,and significant reduction in TIMP—1 level in periph—eral blood of CHF patients .They significantly affect patients＇prognosis ,which may be effective markers predicting prognosis of CHF .