心脏瓣膜疾病所致慢性心衰诊断标志物的筛选及鉴定研究

发布时间：2018-05-07 21:59

本文选题：慢性心力衰竭 + 生物标志物　；参考：《南京医科大学》2015年硕士论文

【摘要】：目的:近年来,慢性心力衰竭的患者数量逐年增多,其生物标志物在心衰的诊断、疗效监测及预后评估方面扮演了越来越重要的角色。本实验通过采集心脏瓣膜病引起的慢性心力衰竭患者与心功能正常患者的血浆样本,分别比较可溶性糖蛋白130(sgp130)、热休克蛋白27(hsp27)、二肽基肽酶4(dpp4)、组织蛋白酶S(ctss)在两组之间的浓度差异,来验证它们是否能作为由心脏瓣膜病所导致的慢性心力衰竭的新的生物标志物,为临床上心衰的早期诊断和治疗提供实验基础。方法:在人体心包液的蛋白质谱系中,通过生物信息学分析,选择四种与心力衰竭相关的蛋白作为候选的待检测标志物。对所有受试者进行12导联心电图、血常规、肾功能、经胸多普勒心脏彩色超声检查。在慢性心衰患者(n=50)心衰症状稳定时采集血液标本,心功能正常对照组(n=50)血液标本采自本中心体检中心。将采集的标本离心、分装供多次检测使用。用Elisa分别检测、对比血浆标本中sgp130、hsp27、dpp4、ctss和氨基端前体脑钠肽(NT-pro-BNP)的浓度,并对所测结果进行统计学分析,评价各候选标志物对由心脏瓣膜病引起的慢性心力衰竭的诊断效能。结果:经过校正临床变量后比较发现,与心功能正常组相比,sgp130(317.3ng/ml vs.215.9ng/ml)、hsp27(2601pg/ml vs.923pg/ml)、NT-pro-BNP(982pg/ml vs.332pg/ml)在慢性心力衰竭患者组中的浓度显著升高(p0.05),而dpp4(7081pg/ml vs.6930pg/ml)、ctss(985pg/ml vs.1050pg/ml)的浓度在两组间无统计学差异。对sgp130、hsp27、NT-pro-BNP进行受试者曲线分析,结果表明在这三种蛋白中,hsp27具有最大的曲线下面积(0.920),是诊断慢性心力衰竭效能最高的独立生物标志物。同时我们将三种标志物进行组合,发现其曲线下面积较独立标志物高(0.969),具有更高的诊断效能。通过比较不同心功能分级之间三种标志物的浓度,发现三种标志物浓度在心功能II级和心功能III-IV级之间无统计学差异。表明这三种标志物可用于慢性心力衰竭的早期诊断。结论:在这项研究中我们验证了sgp130、hsp27以及其与NT-pro-BNP诊断组合可作为有效的生物标志物来诊断心脏瓣膜病引起的慢性心力衰竭。同时,它们对于不同NYHA心功能分级都具有很好的诊断效能,值得进一步的去研究。
[Abstract]:Objective: in recent years, the number of patients with chronic heart failure has increased year by year, and its biomarkers play a more and more important role in the diagnosis, curative effect monitoring and prognosis evaluation of heart failure. The plasma samples of patients with chronic heart failure caused by valvular disease and patients with normal cardiac function were collected to compare the concentrations of soluble glycoprotein 130 sgp130, heat shock protein 27 hsp27, dipeptidyl peptidase 4dpp4, cathepsin Sctssbetween the two groups. To verify whether they can be used as a new biomarker of chronic heart failure caused by valvular disease, and to provide experimental basis for early diagnosis and treatment of heart failure. Methods: in the protein lineage of human pericardial fluid, four proteins related to heart failure were selected as candidate markers by bioinformatics analysis. All subjects were examined by 12-lead electrocardiogram, blood routine, renal function and transthoracic Doppler echocardiography. Blood samples were collected from the patients with chronic heart failure when their symptoms were stable, and the blood samples were collected from the physical examination center of our center in the control group with normal cardiac function. The collected specimens were centrifuged and packed for multiple tests. The concentrations of sgp130 hsp27dpp4ctss and brain natriuretic peptide NT-pro-BNPs were measured by Elisa, and the results were analyzed statistically to evaluate the diagnostic efficacy of each candidate marker for chronic heart failure caused by valvular disease. Results: after adjusting the clinical variables, it was found that the concentration of NT-pro-BNPN 982pgP / ml vs 332pgP / ml in patients with chronic heart failure was significantly higher than that in normal heart failure group (P 0.05), while the concentration of dpp4(7081pg/ml vs.6930pg / ml cttssnctssctssctssctssn985pgrml vs. 1050pgml-1 was not significantly higher than that of normal heart function group (vs.215.9ng-1 / ml), and no significant difference was found between the two groups in the concentration of NT-pro-BNPN 985pgrml vs.1050pgmlml.There was no significant difference between the two groups in the concentration of NT-pro-BNPN 982pg / ml vs.332pgrml-1 / ml in patients with chronic heart failure (CHF), but no significant difference was found between the two groups. The curve analysis of sgp130 hsp27 NT-pro-BNP showed that the hsp27 had the largest area under the curve and was the most effective independent biomarker for the diagnosis of chronic heart failure. At the same time, we combined the three markers and found that the area under the curve was 0.969m higher than that of the independent marker, and had higher diagnostic efficiency. By comparing the concentrations of the three markers among different cardiac function grades, it was found that there was no statistical difference between the concentration of the three markers in the cardiac function grade II and the cardiac function III-IV grade. These three markers can be used in the early diagnosis of chronic heart failure. Conclusion: in this study we demonstrated that sgp130 hsp27 and its combination with NT-pro-BNP can be used as an effective biomarker for the diagnosis of chronic heart failure caused by valvular heart disease. At the same time, they have good diagnostic efficacy for different NYHA cardiac function grades, and are worthy of further study.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R541.6;R542.5

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