摘要
目的探讨重组人脑钠肽(recombinant human brain natriuretic peptide,rhBNP)治疗慢性射血保留型心力衰竭(chronic heart failure with preserved ejection fraction,CHFpEF)并发心房颤动(atrial fibrillation,AF)患者的临床疗效,及其对于心肌纤维化与Janus激酶信号转导和转录激活因子(Janus tyrosine Kinase-signal transducer and activator of transcription 3,JAK/STAT3)信号通路相关指标的影响。方法选取自2020年2月至2022年3月于邢台市中心医院就诊的115例CHFpEF并发AF的患者,根据随机数字表法分为常规治疗组(n=58)与研究治疗组(n=57)。常规治疗组患者予以基础治疗,包括吸氧、心电监护、给予利尿和扩血管等药物、控制心室率及抗凝治疗。研究治疗组患者在常规治疗组的基础上给予rhBNP治疗。比较两组患者的临床疗效[氨基末端脑钠肽前体(amino-terminal pro-B-type natriuretic peptide,NT-proBNP)、左心室射血分数(left ventricular ejection fraction,LVEF)、6 min步行距离(6 minutes walking distance,6MWT)、纽约心脏协会(New York Heart Association,NYHA)心功能分级以及主要不良心血管事件(急性冠状动脉综合征、心力衰竭再次住院率、病死率)等发生情况]、凝血功能[D-二聚体(D-dimer,D-D)及凝血酶原时间(prothrombin time,PT)]、心肌纤维化标志物浓度[透明质酸(hyaluronic acid,HA)、层黏连蛋白(laminin,LN)、结缔组织生长因子(connective tissue growth factor,CTGF)、III型前胶原氨基末前端肽(eukaryotic procollagenIIIN-terminal propeptide,PIIINP)]及JAK/STAT3信号通路相关指标[磷酸化酪氨酸激酶2(phosphorylated tyrosine kinase 2,P-JAK2)、磷酸化信号转导和转录激活蛋白(phosphorylated signal transduction and transcription activator protein,P-STAT)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)]。结果两组患者的一般资料比较,差异均无统计学意义(P>0.05)。常规治疗组与研究治疗组患者的显效率分别为50.00%、70.18%,治疗总有效率分别为84.48%、100%,且研究治疗组均显著高于常规治疗组,差异有统计学意义(χ^(2)=4.876,P=0.027;χ^(2)=9.596,P=0.002)。两组患者的主要不良心血管事件发生率比较,差异无统计学意义(P>0.05)。治疗20 d后两组患者的NT-proBNP、D-D浓度均降低,且研究治疗组显著低于常规治疗组,差异有统计学意义(χ^(2)=2.892,P=0.005;χ^(2)=2.046,P=0.043)。治疗20 d后两组患者的的LVEF、6MWT、PT均增加,且研究治疗组显著高于常规治疗组,差异有统计学意义(χ^(2)=2.103,P=0.038;χ^(2)=11.197,P<0.001;χ^(2)=2.003,P=0.048)。治疗20 d后两组患者的的HA、LN、GTGF、PIIINP浓度计均降低,且研究治疗组明显低于常规治疗组,差异有统计学意义(χ^(2)=11.150,P<0.001;χ^(2)=10.595,P<0.001;χ^(2)=5.859,P<0.001;χ^(2)=20.823,P<0.001)。治疗20 d后,研究治疗组患者的的P-JAK2相对表达量、P-STAT3相对表达量及α-SMA相对表达量均明显低于常规治疗组,差异有统计学意义(χ^(2)=7.098,P<0.001;χ^(2)=10.602,P<0.001;χ^(2)=9.464,P<0.001)。结论rhBNP治疗CHFpEF并发AF患者的疗效较好,能够通过下调JAK/STAT3信号通路的激活抑制制心肌纤维化相关因子的释放,从而抑制心肌纤维化进程,改善CHFpEF并发AF患者的心功能与凝血功能。
Objectives To investigate the clinical efficacy of recombinant human brain natriuretic peptide(rhBNP)in the treatment of patients with chronic heart failure with preserved ejection fraction(CHFpEF)combined with atrial fibrillation(AF)and its effect on myocardial fibrosis associated with Janus tyrosine Kinase-signal transducer and activator of transcription 3(JAK/STAT3)signaling pathway-related indexes.Methods Totally 115 patietns with CHFPEF combined with AF were selected from February 2020 to March 2022 in Xingtai Central Hospital.According to random number table method,the patients were divided into conventional treatment group(n=58)and study treatment group(n=57).Patients in conventional treatment group received basic treatment,including oxygen therapy,electrocardiographic monitoring,administration of diuretics and vasodilators,control of ventricular rate,and anticoagulant therapy.Patients in study treatment group were treated with rhBNP in addition to conventional treatment group.The clinical efficacy[amino terminal pro-B-type natriuretic peptide(NT-proBNP)],left ventricular ejection fraction(LVEF),6-minute walking distance(6MWT),New York Heart Association(NYHA)functional classification,major adverse cardiovascular events(acute coronary syndrome,readmission rate for heart failure,mortality rate),coagulation function[D-dimer(D-D)and prothrombin time(PT)],myocardial fibrosis markers,concentrations of substances[hyaluronic acid(HA),laminin(LN),connective tissue growth factor(CTGF),TypeⅢprocollagen N-terminal peptide(PⅢNP)]and JAK/STAT3 signaling pathway related indicators[phosphorylated tyrosine kinase 2(P-JAK2),phosphorylated signal transduction and transcription activator protein(P-STAT),α-smooth muscle actin(α-SMA)]of the two groups were compared.Results The difference between the general information of the two groups was not statistically significant(P>0.05).The significant effective rates of conventional treatment group and study treatment group were 50.00%and 70.18%,respectively,and the total effective rates were 84.48%and 100%,respectively,which in study treatment group were significantly higher than those of conventional treatment group(χ^(2)=4.876,P=0.027;χ^(2)=9.596,P=0.002).The difference in major adverse cardiovascular events between the two groups was not statistically significant(P>0.05).Concentrations of NT-proBNP and D-D were reduced after 20 d of treatment,and which in study treatment group were significantly lower than those in conventional treatment group(χ^(2)=2.892,P=0.005;χ^(2)=2.046,P=0.043).LVEF,6MWT and PT increased after 20 d of treatment,and which in study treatment group were significantly higher than those in conventional treatment group(χ^(2)=2.103,P=0.038;χ^(2)=11.197,P<0.001;χ^(2)=2.003,P=0.048).The concentrations of HA,LN,GTGF,and PⅢNP were decreased after 20 d of treatment,and which in study treatment group were significantly lower than those in conventional treatment group(χ^(2)=11.150,P<0.001;χ^(2)=10.595,P<0.001;χ^(2)=5.859,P<0.001;χ^(2)=20.823,P<0.001).The relative expression of P-JAK2,the relative expression of P-STAT3 and the relative expression ofα-SMA in study treatment group were significantly lower than those of conventional treatment group after 20 d of treatment(χ^(2)=7.098,P<0.001;χ^(2)=10.602,P<0.001;χ^(2)=9.464,P<0.001).Conclusions rhBNP is effective in the treatment of patients with CHFpEF combined with AF,and can inhibit the release of myocardial fibrosis-related factors by down-regulating the activation of JAK/STAT3 signaling pathway,thereby inhibiting the process of myocardial fibrosis,and improving the cardiac function and coagulation function.
作者
狄宁宁
达迎晓
周松
黄玲芳
DI Ningning;DA Yingxiao;ZHOU Song;HUANG Lingfang(Department of Cardiology,Xingtai Central Hospital,Xingtai,Hebei 054500,China)
出处
《岭南心血管病杂志》
2025年第5期472-480,共9页
South China Journal of Cardiovascular Diseases
基金
河北省重点研发计划项目(项目编号:20209499815D)。
关键词
心力衰竭
重组人脑钠肽
心房颤动
心肌纤维化
Janus激酶信号转导和转录激活因子信号通路因子
heart failure
recombinant human brain natriuretic peptide
atrial fibrillation
myocardial fibrosis
indexes of Janus tyrosine Kinase-signal transducer and activator of transcription 3 signaling pathway
