循环微小RNA-133a、半乳糖凝集素-3在慢型克山病与扩张型心肌病中的差异表达及临床应用价值

摘要

目的 探讨慢型克山病和扩张型心肌病患者外周血中微小RNA(miR)-133a、半乳糖凝集素-3(Galectin-3)的差异表达水平及在临床鉴别诊断中的应用价值.方法 在黑龙江省克山病历史重病区,选取慢型克山病患者、健康人(对照)各28例;同时在非病区选取扩张型心肌病患者28例.记录年龄、性别,进行病史询问和体格检查,并使用多普勒心脏超声测定左心室射血分数(LVEF)与左心室舒张末期内径(LVEDD);收集血样(肘部静脉),分别采用实时荧光定量PCR技术和酶联免疫吸附法测定各组研究对象血浆miR-133a、血清Galectin-3的表达水平.同时分析miR-133a、Galectin-3、LVEF、LVEDD间的相关性.结果 各组间miR-133a、Galectin-3表达水平比较差异有统计学意义(F=48.789、9.485,P均＜0.01).慢型克山病组和扩张型心肌病组miR-133a表达水平[中位数(四分位数):0.394(0.271,0.770)、1.665(0.943,2.713)]均低于对照组[2.382(1.502,3.302),P＜0.01或＜0.05],且慢型克山病组miR-133a表达水平低于扩张型心肌病组(P＜ 0.01);慢型克山病组和扩张型心肌病组Galectin-3表达水平[17.710(9.624,27.799)、12.692(9.376,26.290)μg/L]比较差异无统计学意义(P＞0.05),但均显著高于对照组[8.070(7.135,9.308)μg/L,P均＜0.01].miR-133a与LVEF呈正相关(rs=0.297,P＜ 0.01),与LVEDD、Galectin-3呈负相关性(rs=-0.271、-0.318,P＜0.05或＜0.01);Galectin-3与LVEF呈负相关(rs=-0392,P＜0.01),与LVEDD呈正相关(rs=0385,P＜0.01).结论 miR-133a与Galectin-3、LVEF、LVEDD联用可为慢型克山病与扩张型心肌病临床鉴别诊断提供帮助.%Objective To explore expression level of circulating microRNA (miR)-133a and Galectin-3 and their potential clinical application in differential diagnosis between patients with chronic Keshan disease and dilated cardiomyopathy.Methods Twenty-eight patients with chronic Keshan disease and 28 cases of age-and sex-matched healthy people as control from the same severe historical endemic areas of Keshan disease in Heilongjiang Province,and another 28 patients with dilated cardiomyopathy from non-affected areas were chosen for the study.All the subjects were asked for disease history and did physical examination,examined by Doppler echocardiography for left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD),and collected fasting venous blood specimen (elbow vein).The plasma miR-133a and the serum Galectin-3 were determined by Real-time PCR and enzyme-linked immunosorbent method,respectively.Meanwhile,the correlation was analyzed between miR-133a,galectin-3,LVEF and LVEDD.Results The miR-133a and Galectin-3 levels in different groups were statistically different (F =48.789,9.485,P ＜ 0.01).The plasma miR-133a level in chronic Keshan disease group and dilated cardiomyopathy group [median (quartile):0.394 (0.271,0.770),1.665 (0.943,2.713)] were both significantly lower than those in control group [2.382 (1.502,3.302],P ＜ 0.01 or ＜ 0.05],and the plasma miR-133a level in chronic Keshan disease group was lower than that in dilated cardiomyopathy group (P ＜ 0.01).There was no significant difference of serum Galectin-3 level between chronic Keshan disease group and dilated cardiomyopathy group [17.710 (9.624,27.799),12.692 (9.376,26.290) μg/L,P ＞ 0.05],but both were significantly higher than those in control group [8.070 (7.135,9.308) μg/L,P ＜ 0.01].The miR-133a was positively correlated with LVEF (rs =0.297,P ＜ 0.01),while negatively correlated with LVEDD,and Galectin-3 (rs =-0.271,-0.318,P ＜ 0.05 or ＜ 0.01);the serum Galectin-3 was negatively correlated with LVEF (rs =-0.392,P ＜ 0.01),and positively correlated with LVEDD (rs =0.385,P ＜ 0.01).Conclusion The combined application of miR-133a,Galectin-3,LVEF and LVEDD may provide assistance in clinical differential diagnosis of chronic Keshan disease and dilated cardiomyopathy.