摘要
目的 :探讨慢性心力衰竭(CHF)患者血清中微小RNA-21(miR-21)及组织基质金属蛋白酶抑制剂-3(TIMP3)的表达及其与心肌重构和心功能的相关性。方法:CHF患者114例,按《慢性心力衰竭诊断治疗指南》心功能分级:Ⅰ~Ⅱ级35例、Ⅲ级40例、Ⅳ级39例。另选取同期体检健康者40例为对照组。采用超声心动图测定左室舒张末内径(LVEDD)、左心房内径(LAD)、左心室后壁厚度(LVPW)、左室质量指数(LVMI)、左室重构指数(LVRI),利用二维上平面法检测心输出量(CO)和左室射血分数(LVEF),采用qRT-PCR法检测血清miR-21及TIMP3 mRNA水平,采用免疫层析法检测血清心衰标志物NT-proBNP水平。结果:各组间miR-126表达水平比较,差异有统计学意义(P<0.01);CHF患者miR-126表达高于对照组,差异有统计学意义(P<0.05);CHF心功能各级患者miR-126表达高于对照组,差异均有统计学意义(P<0.05);随着心功能分级的提高,miR-126表达逐渐增加,其中Ⅳ级患者高于Ⅲ级患者,差异有统计学意义(P<0.05)。各组间TIMP3表达水平比较,差异有统计学意义(P<0.01)。CHF患者TIMP3表达低于对照组,差异有统计学意义(P<0.05);CHF心功能各级患者TIMP3表达低于对照组,差异均有统计学意义(P<0.05),且Ⅳ级<Ⅲ级<Ⅰ~Ⅱ级,差异均有统计学意义(P<0.05)。与对照组比较,CHF各心功能组LVPW、LVMI升高,CO、LVER、NT-proBNP降低,Ⅲ级、Ⅳ级LVEDD、LAD升高,LVRI降低,差异均有统计学意义(P<0.05);CHF组LVEDD、LAD、LVPW、LVMI、NT-proBNP随心功能分级升高而升高,LVRI、CO、LVER随心功能分级降低而降低。Pearson相关分析显示,miR-21与TIMP3呈负相关(r=-0.719,P=0.006)。miR-21与LVEDD、LVPW、NT-proBNP呈显著正相关(r=0.624,0.593,0.671,P<0.05),与LAD呈一般正相关(r=0.476,P<0.05),与LVMI无明显相关性(r=0.193,P>0.05),与LVRI、CO、LVER呈显著负相关(r=-0.624,-0.509,-0.602,P<0.05);TIMP3与LVEDD、LVMI呈显著负相关(r=-0.537,-0.596,P <0.05),与LVPW呈一般负相关(r=-0.436,P <0.05),与LVRI、LVER、NT-proBNP呈显著正相关(r=0.613,0.674,0.693,P<0.05),与LAD、CO无显著相关性(r=-0.264,0.126,P>0.05)。结论:CHF患者血清miR-21高表达,TIMP3低表达,与心肌重构及心功能有一定相关性,可作为评估CHF发生发展指标。
Objective:To investigate the expression of microRNA-21(miR-21)and tissue matrix of metalloproteinase inhibitor-3(TIMP3)in serum of patients with chronic heart failure(CHF)and their correlation with myocardial remodeling and cardiac function.Method:According to the guideline for diagnosis and treatment of chronic heart failure,the cardiac function of 114 patients with CHF was classified into 35 patients of Grade I-II,40 patients of GradeⅢand 39 patients of GradeⅣ.In addition,40 healthy people in the same period were selected as the control group.Left ventricular end diastolic diameter(LVEDd),left atrial diameter(LAD),left posterior wall thickness(LVPW),left ventricular mass index(LVMI),left ventricular remodeling index(LVRI)were measured by echocardiography,the cardiac output(CO)and left ventricular ejection fraction(LVEF)were measured by two-dimensional upper plane method.The levels of miR-21 and TIMP3 mRNA in serum were measured by qRT-PCR,and the level of NT proBNP,a marker of heart failure,was measured by immunochromatography.Result:The expression level of miR-126 in each group was significantly different(P<0.01);the expression of miR-126 in CHF patients was significantly higher than that in the healthy control group,the difference was significant(P<0.05);the expression of miR-126 in CHF patients at all levels of cardiac function was significantly higher than that in the healthy control group,the difference was significant(P<0.05);The expression of miR-126 increased with the improvement of cardiac function grade,and the level of patients with Grade IV was higher than that of patients with Grade III,the difference was significant(P<0.05).The expression level of TIMP3 in each group was significantly different(P<0.01).The expression of TIMP3 in CHF patients was lower than that in the healthy control group,the difference was significant(P<0.05);the expression of TIMP3 in patients with CHF at all levels of cardiac function was lower than that in the healthy control group,the difference was statistically significant(P<0.05),and Level IV<Level III<Level I-II,the difference was statistically significant(P<0.05).Compared with the control group,LVPW and LVMI increased,CO,LVER and NT-proBNP decreased in each CHF heart function group,LVEDD and LAD increased and LVRI decreased of GradeⅢandⅣ,the difference was statistically significant(P<0.05);LVEDD,LAD,LVPW,LVMI,NT-proBNP increased with the increase of heart function grade in the CHF group,while LVRI,CO,LVER decreased with the decrease of the heart function grade.Pearson correlation analysis showed that miR-21 was negatively correlated with TIMP3(r=-0.719,P=0.006).miR-21 had a significant positive correlation with LVEDD,LVPW,NT-proBNP(r=0.624,0.593,0.671,P<0.05),a general positive correlation with LAD(r=0.476,P<0.05),no significant correlation with LVMI(r=0.193,P>0.05),and a significant negative correlation with LVRI,CO,LVER(r=-0.624,-0.509,-0.602,P<0.05);TIMP3 had a significant negative correlation with LVEDD and LVMI(r=-0.537,-0.596,P<0.05),a general negative correlation with LVPW(r=-0.436,P<0.05),a significant positive correlation with LVRI,LVER,NT-proBNP(r=0.613,0.674,0.693,P<0.05),and no significant correlation with LAD and CO(r=-0.264,0.126,P>0.05).Conclusion:The high expression of miR-21 and the low expression of TIMP3 in serum of CHF patients were related to myocardial remodeling and cardiac function,which can be used as an index to evaluate the occurrence and development of CHF.
作者
陈旭杰
罗明
CHEN Xujie;LUO Ming(Department of Cardiovascular Diseases,Nanyang Second People’s Hospital,Henan 473000;Department of Obstetrics and Gynecology,Nanyang Second People’s Hospital,Henan 473000)
出处
《交通医学》
2020年第3期230-234,共5页
Medical Journal of Communications
