【摘要】 目的 分析慢性心力衰竭(CHF)患者血浆外泌体长链非编码RNA H19(LncRNA H19)、微小RNA-214(miR-214)表达与血清炎性因子和左心室重构的关系。方法 选取2020年7月—2022年9月内蒙古自治区人民医院心血管内科收治CHF患者120例为CHF组，另选取同期医院体检健康志愿者40例为健康对照组。采用实时荧光定量聚合酶链式反应检测血浆外泌体LncRNA H19、miR-214表达，酶联免疫吸附法检测炎性因子[白介素(IL)-1β、IL-6、IL-18、肿瘤坏死因子-α(TNF-α)]水平，超声心动图检测左心室重构指标[左心室舒张末期内径(LVEDD)、左心室后壁厚度(LVPWT)、舒张末期室间隔厚度(IVST)和左心室心肌质量指数(LVMI)]。通过StarBase数据库预测LncRNA H19与miR-214的关系。采用Pearson/Spearman相关性分析CHF患者血浆外泌体LncRNA H19、miR-214表达与纽约心脏病协会(NYHA)心功能分级、炎性因子和左心室重构指标的相关性。绘制受试者工作特征曲线(ROC)获得血浆外泌体LncRNA H19、miR-214预测CHF患者发生左心室重构的效能。结果 与健康对照组比较，CHF组血浆外泌体LncRNA H19表达和血清IL-1β、IL-6、IL-18、TNF-α水平及LVEDD、LVPWT、IVST、LVMI升高，miR-214表达降低(t=15.837、93.717、86.669、103.761、76.500、9.953、29.647、30.652、13.832、11.256,P均<0.001)。NYHA心功能分级Ⅱ级、Ⅲ级、Ⅳ级CHF患者血浆外泌体LncRNA H19表达和血清IL-1β、IL-6、IL-18、TNF-α水平及LVEDD、LVPWT、IVST、LVMI依次升高，miR-214表达依次降低(F=247.164、182.669、259.385、298.349、235.816、196.860、171.320、182.099、179.760、138.863,P均<0.001)。经StarBase数据库预测，LncRNA H19与miR-214存在互补序列。Pearson/Spearman相关性分析显示，CHF患者血浆外泌体LncRNA H19与IL-1β、IL-6、IL-18、TNF-α、NYHA心功能分级、LVEDD、LVPWT、IVST、LVMI呈正相关，与miR-214呈负相关(r=0.739、0.774、0.789、0.767、0.899、0.753、0.735、0.743、0.752、-0.885,P均<0.001);miR-214与IL-1β、IL-6、IL-18、TNF-α、NYHA心功能分级、LVEDD、LVPWT、IVST、LVMI呈负相关(r=-0.785、-0.783、-0.779、-0.773、-0.839、-0.761、-0.767、-0.745、-0.751、-0.885,P均<0.001)。血浆外泌体LncRNA H19、miR-214及二项联合预测左心室重构的曲线下面积(AUC)分别为0.780、0.779、0.877,二项联合的AUC高于单项预测(Z=3.026、3.114,P=0.003、0.002)。结论 CHF患者血浆外泌体LncRNA H19高表达，miR-214低表达，与CHF患者炎性反应和左心室重构密切相关，可能成为CHF患者病情严重程度和左心室重构的评估指标。更多还原

【Abstract】 Objective To analyze the relationship between the expression of long chain non coding RNA H19(LncRNA H19) and microRNA-214(miR-214) in plasma extracellular vesicles of patients with chronic heart failure(CHF), inflammatory factors, and left ventricular remodeling. Methods From July 2020 to September 2022, 120 CHF patients were selected as the CHF group, and 40 healthy volunteers were selected as the healthy control group. The expression of LncRNA H19 and miR-214 in plasma exosomes was detected by real-time fluorescence quantitative Polymerase chain reaction, and the inflammatory factor [interleukin(IL)-1 was detected by enzyme-linked immunosorbent assay β, IL-6, IL-18, Tumor Necrosis Factor-α(TNF-α)] Horizontal, echocardiographic detection of left ventricular remodeling indicators [left ventricular end diastolic diameter(LVEDD), left ventricular posterior wall thickness(LVPWT), end diastolic interventricular septal thickness(IVST), and left ventricular myocardial mass index(LVMI)]. Predict the relationship between LncRNA H19 and miR-214 through the StarBase database. Pearson/Spearman correlation analysis was used to investigate the correlation between the expression of plasma exosomes LncRNA H19 and miR-214 in CHF patients and the New York Heart Association(NYHA) cardiac function grading, inflammatory factors, and left ventricular remodeling indicators. Draw the receiver operating characteristic curve(ROC) to obtain the efficacy of plasma extracellular vesicles LncRNA H19 and miR-214 in predicting left ventricular remodeling in CHF patients. Results Compared with the healthy control group, the CHF group showed plasma exosomes LncRNA H19 expression and serum IL-1 β, IL-6, IL-18, TNF-α, and LVEDD, LVPWT, IVST, and LVMI increased, while the expression of miR-214 decreased(t=15.837, 93.717, 86.669, 103.761, 76.500, 9.953, 29.647, 30.652, 13.832, 11.256, all P<0.001). The expression of plasma extracellular LncRNA H19 and serum IL-1 in patients with NYHA grade II, III, and IV CHF β, IL-6, IL-18, TNF-α, the levels of LVEDD, LVPWT, IVST, and LVMI increased sequentially, while the expression of miR-214 decreased sequentially(F=247.164, 182.669, 259.385, 298.349, 235.816, 196.860, 171.320, 182.099, 179.760, 138.863, all P<0.001). According to the StarBase database prediction, there is a complementary sequence between LncRNA H19 and miR-214. Pearson/Spearman correlation analysis showed that plasma exosomes LncRNA H19 and IL-1 in CHF patients β, IL-6, IL-18, TNF-α, NYHA cardiac function grading, LVEDD, LVPWT, IVST, LVMI were positively correlated, but negatively correlated with miR-214(r=0.739, 0.774, 0.789, 0.767, 0.899, 0.753, 0.735, 0.743, 0.752,-0.885, P<0.001); miR-214 and IL-1 β, IL-6, IL-18, TNF-α, NYHA cardiac function grading, LVEDD, LVPWT, IVST, and LVMI were negatively correlated(r=-0.785,-0.783,-0.779,-0.773,-0.839,-0.761,-0.767,-0.745,-0.751,-0.885, all P<0.001). The area under the curve(AUC) of plasma extracellular vesicles LncRNA H19, miR-214, and binomial combination for predicting left ventricular remodeling were 0.780, 0.779, and 0.877, respectively. The AUC of binomial combination was higher than that of single prediction(Z=3.026, 3.114, P=0.003, 0.002). Conclusion The high expression of LncRNA H19 and low expression of miR-214 in plasma exosomes of CHF patients are closely related to inflammatory response and left ventricular remodeling, and may become an evaluation index for the severity of CHF patients’ condition and left ventricular remodeling.更多还原