血清微小RNA-29c-3p和微小RNA-378a-3p表达与脓毒症心肌损伤患者血清炎性因子、心肌损伤指标和超声心动图指标的相关性及对预后的评估价值

Correlation between the expressions of serum microRNA-29c-3p,microRNA-378a-3p and serum inflammatory factors,myocardial injury indexes and echocardiographic indexes in sepsis patients with myocardial injury and the value of prognosis evaluation

目的探讨血清微小RNA(miR)-29c-3p和miR-378a-3p表达与脓毒症心肌损伤患者血清炎性因子、心肌损伤指标和超声心动图指标的相关性,分析其对预后的评估价值。方法采用前瞻性的研究方法。选择2019年2月至2021年10月邯郸市中心医院脓毒症患者286例,采用聚合酶链反应检测血清miR-29c-3p和miR-378a-3p水平,并检测血清肌钙蛋白I(TnI)、肌酸激酶同工酶MB(CK-MB)、肌红蛋白(Mb)、B型脑钠肽(BNP)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)和降钙素原(PCT)水平;采用超声检测左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)、每搏输出量(SV)、心输出量(CO)和二尖瓣口舒张早期最大流速与心房收缩期最大流速比值(E/A)。将血清TnI≥0.15 μg/L定义为心肌损伤,记录心肌损伤患者住院28 d内生存情况,并评估急性生理学和慢性健康状况Ⅱ评分(APACHE Ⅱ)和序贯器官衰竭评分(SOFA)。采用Pearson法进行相关性分析;采用多因素Logistic回归分析影响脓毒症心肌损伤患者住院28 d内死亡的独立危险因素;绘制受试者工作特征(ROC)曲线,分析miR-29c-3p和miR-378a-3p预测脓毒症心肌损伤患者住院28 d内死亡的效能。结果 286例脓毒症患者中,发生心肌损伤131例(心肌损伤组),未发生心肌损伤155例(无心肌损伤组)。心肌损伤组miR-29c-3p、Mb、CK-MB、BNP、TnI、TNF-α、IL-6、IL-1β、PCT、CRP、LVEDD和LVESD明显高于无心肌损伤组[5.02 ± 1.69比2.01 ± 0.57、(102.35 ± 23.56) μg/L比(32.15 ± 9.12) μg/L、(25.01 ± 6.09) U/L比(13.02 ± 4.16) U/L、(905.23 ± 135.49) ng/L比(92.31 ± 26.35)ng/L、(0.23 ± 0.05)μg/L比(0.12 ± 0.02)μg/L、(13.41 ± 3.71)μg/L比(3.26 ± 0.95)μg/L、(9.02 ± 2.46)ng/L比(4.18 ± 1.03)ng/L、(71.45 ± 15.29)ng/L比(30.02 ± 6.39)ng/L、(1.05 ± 0.21)μg/L比(0.72 ± 0.13)μg/L、(21.35 ± 6.13)mg/L比(16.23 ± 4.57)mg/L、(37.45 ± 3.39)mm比(34.01 ± 2.15)mm和(50.12 ± 3.49)mm比(44.17 ± 3.02)mm],miR-378a-3p、LVEF、SV、CO和E/A明显低于无心肌损伤组[1.67 ± 0.36比3.02 ± 0.79、(46.32 ± 3.26)%比(56.24 ± 4.98)%、(48.21 ± 2.81)ml比(56.02 ± 3.49)ml、(3.11 ± 0.29)L/min比(4.15 ± 0.31)L/min和0.98 ± 0.21比1.19 ± 0.32],差异有统计学意义(P<0.01)。Pearson相关分析结果显示,脓毒症心肌损伤患者miR-29c-3p与TNF-α、IL-6、IL-1β、PCT、CRP、Mb、CK-MB、BNP、TnI、LVEDD、LVESD呈正相关(P<0.01或<0.05),与LVEF、SV、CO和E/A呈负相关(P<0.01);miR-378a-3p与TNF-α、IL-6、IL-1β、PCT、CRP、Mb、CK-MB、BNP、TnI、LVEDD和LVESD呈负相关(P<0.01或<0.05),与LVEF、SV、CO和E/A呈正相关(P<0.01)。131例脓毒症心肌损伤患者住院28 d内死亡55例(死亡亚组),存活76例(存活亚组)。死亡亚组机械通气率、连续性肾脏替代治疗率、APACHE Ⅱ、SOFA、miR-29c-3p、Mb、CK-MB、TnI、BNP、TNF-α、IL-6、IL-1β、PCT、CRP、LVEDD和LVESD明显高于存活亚组,miR-378a-3p、LVEF、SV、CO和E/A明显低于存活亚组,差异有统计学意义(P<0.05或<0.01)。多因素Logistic回归分析结果显示,APACHE Ⅱ、TnI、miR-29c-3p是影响脓毒症心肌损伤患者住院28 d内死亡的独立危险因素(OR = 1.203、2.451和1.394,95%CI 1.085~1.334、1.498~4.008和1.141~1.702,P<0.01),miR-378a-3p是影响脓毒症心肌损伤患者住院28 d内死亡的独立保护因素(OR = 0.367,95%CI 0.217~0.622,P<0.01)。ROC曲线分析结果显示,miR-29c-3p和miR-378a-3p预测脓毒症心肌损伤患者住院28 d内死亡的最佳截断值分别为5.00和1.65,miR-29c-3p联合miR-378a-3p预测脓毒症心肌损伤患者住院28 d内死亡的曲线下面积明显大于两项指标单独应用(0.890比0.695和0.732),灵敏度为87.0%,特异度为87.3%,准确度为86.8%。结论脓毒症心肌损伤患者血清miR-29c-3p表达水平升高、miR-378a-3p表达水平降低,miR-29c-3p和miR-378a-3p表达与心肌损伤程度、超声心动图指标、炎性因子水平以及预后均有关,miR-29c-3p和miR-378a-3p可作为评估脓毒症心肌损伤患者预后的潜在指标。

Objective To investigate the correlation between the expressions of microRNA(miR)-29c-3p,miR-378a-3p and serum inflammatory factors,myocardial injury indexes and echocardiographic indexes in sepsis patients with myocardial injury,and analyze the value of prognosis evaluation.Methods Prospective research methods were used.Two hundred and eighty-six patients with sepsis in Handan Central Hospital from February 2019 to October 2021 were selected.The serum levels of miR-29c-3p and miR-378a-3p were detected by polymerase chain reaction,and serum Troponin I(TnI),creatine kinase isoenzyme MB(CK-MB),myoglobin(Mb),B-type brain natriuretic peptide(BNP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and procalcitonin(PCT)were detected.The left ventricular end diastolic diameter(LVEDD),left ventricular end systolic diameter(LVESD),left ventricular ejection fraction(LVEF),stroke output(SV),cardiac output(CO)and the ratio of early diastolic maximum mitral valve velocity to atrial systolic maximum velocity(E/A)were measured by echocardiography.Serum TnI≥0.15μg/L was defined as myocardial injury,the survival status within 28 d of hospitalization in patients with myocardial injury was recorded,and the acute physiology and chronic healthⅡevaluation(APACHEⅡ)and sequential organ failure assessment(SOFA)were evaluated.Pearson method was used for correlation analysis;Multivariate Logistic regression was used to analyze the independent risk factors of death within 28 d of hospitalization in sepsis patients with myocardial injury;the receiver operating characteristic(ROC)curve was drawn to analyze the efficacy of miR-29c-3p and miR-378a-3p in predicting the death within 28 d of hospitalization in septic patents with myocardial injury patients.Results Among 286 patients with sepsis,131 had myocardial injury(myocardial injury group),and 155 had no myocardial injury(non-myocardial injury group).The miR-29c-3p,Mb,CK-MB,BNP,TnI,TNF-α,IL-6,IL-1β,PCT,CRP,LVEDD and LVESD in myocardial injury group were significantly higher than those in non-myocardial injury group:5.02±1.69 vs.2.01±0.57,(102.35±23.56)μg/L vs.(32.15±9.12)μg/L,(25.01±6.09)U/L vs.(13.02±4.16)U/L,(905.23±135.49)ng/L vs.(92.31±26.35)ng/L,(0.23±0.05)μg/L vs.(0.12±0.02)μg/L,(13.41±3.71)μg/L vs.(3.26±0.95)μg/L,(9.02±2.46)ng/L vs.(4.18±1.03)ng/L,(71.45±15.29)ng/L vs.(30.02±6.39)ng/L,(1.05±0.21)μg/L vs.(0.72±0.13)μg/L,(21.35±6.13)mg/L vs.(16.23±4.57)mg/L,(37.45±3.39)mm vs.(34.01±2.15)mm and(50.12±3.49)mm vs.(44.17±3.02)mm,the miR-378a-3p,LVEF,SV,CO and E/A were significantly lower than those in non-myocardial injury group:1.67±0.36 vs.3.02±0.79,(46.32±3.26)%vs.(56.24±4.98)%,(48.21±2.81)ml vs.(56.02±3.49)ml,(3.11±0.29)L/min vs.(4.15±0.31)L/min and 0.98±0.21 vs.1.19±0.32,and there were statistical differences(P<0.01).Pearson correlation analysis result showed that miR-29c-3p was positive correlation with TNF-α,IL-6,IL-1β,PCT,CRP,Mb,CK-MB,BNP,TnI,LVEDD and LVESD in sepsis patients with myocardial injury(P<0.01 or<0.05),and it was negative correlation with LVEF,SV,CO and E/A(P<0.01);miR-378a-3p was negative correlation with TNF-α,IL-6,IL-1β,PCT,CRP,Mb,CK-MB,BNP,TnI,LVEDD and LVESD(P<0.01 or<0.05),and it was positive correlation with LVEF,SV,CO and E/A P<0.01).Among 131 sepsis patients with myocardial injury,55 patients died within 28 d of hospitalization(death subgroup),and 76 patients survived(survival subgroup).The mechanical ventilation rate,continuous renal replacement therapy rate,APACHEⅡ,SOFA,miR-29c-3p,Mb,CK-MB,TnI,BNP,TNF-α,IL-6,IL-1β,PCT,CRP,LVEDD and LVESD in death subgroup were significantly higher than those in survival subgroup,the miR-378a-3p,LVEF,SV,CO and E/A were significantly lower than those in survival subgroup,and there were statistical differences(P<0.05 or<0.01).Multivariate Logistic regression analysis result showed that APACHEⅡ,TnI,miR-29c-3p were independent risk factors for death within 28 d of hospitalization in sepsis patients with myocardial injury(OR=1.203,2.451 and 1.394;95%CI 1.085 to 1.334,1.498 to 4.008 and 1.141 to 1.702;P<0.01);and the miR-378a-3p an independent protective factor for death within 28 d of hospitalization in sepsis patients with myocardial injury(OR=0.367,95%CI 0.217 to 0.622,P<0.01).ROC curve analysis result show that the best cut-off values of miR-29c-3p and miR-378a-3p for predicting the death within 28 d of hospitalization in sepsis patients with myocardial injury were 5.00 and 1.65;the area under the curve of miR-29c-3p combined with miR-378a-3p for predicting the death within 28 d of hospitalization in septic patients with myocardial injury was significantly larger than that of the two separate applications(0.890 vs.0.695 and 0.732),with a sensitivity of 87.0%,a specificity of 87.3%,and an accuracy of 86.8%.Conclusions The expression of serum miR-29c-3p is increased and the expression of miR-378a-3p is decreased in sepsis patients with myocardial injury.The expressions of miR-29c-3p and miR-378a-3p are related to the degree of myocardial injury,echocardiogram indexes,the levels of inflammatory factors and prognosis.The miR-29c-3p and miR-378a-3p can be used as potential prognostic indexes for sepsis patients with myocardial injury.