伊伐布雷定对慢性心力衰竭患者外周血单核细胞中TLR-4及NF-κB表达的影响研究

Influence of ivabradine on expressions of peripheral blood mononuclear Toll-like receptor 4 and nuclear factor-κB in patients with chronic heart failure

目的探究伊伐布雷定对慢性心力衰竭患者外周血单核细胞Toll样受体4(TLR-4)及核转录因子B(NF-κB)表达的影响。方法根据随机数字表法将2020年1月至2023年1月于成都市第三人民医院心内科收治的120例慢性心力衰竭患者,分为对照组和实验组,每组各60例。对照组在常规治疗的基础上予以美托洛尔治疗(初次口服12.5 mg,qd,每间隔一周将药量增加12.5 mg,每日最大剂量不得超过50 mg),实验组在对照组的基础上加用伊伐布雷定治疗(初次口服2.5 mg,bid,根据患者心率调整用量),连续治疗3个月。比较两组患者治疗前、后心功能指标如左心室射血分数(LVEF)、左心室收缩末期内径(LVESD)及左心室舒张末期内径(LVEDD)、6 min步行试验距离(6MWD)等,血清炎症因子N末端脑钠肽前体(NT-proBNP)、心肌肌钙蛋白T(cTnT)、基质金属蛋白酶-9(MMP-9)水平以及TLR-4、NF-κB的mRNA表达水平,比较两组患者临床疗效以及不良反应发生率。结果治疗前两组临床指标无统计学差异(P>0.05)。与治疗前相比,两组治疗后LVEF和6MWD均升高(P<0.05)且实验组LVEF和6MWD均高于对照组(P<0.05),两组治疗后LVESD、LVEDD均下降(P<0.05)且实验组LVESD、LVEDD均低于对照组(P<0.05)。治疗前两组血清炎症因子水平无统计学差异(P>0.05)。与治疗前相比,两组治疗后NT-proBNP、cTnT、MMP-9均下降(P<0.05),且治疗后实验组NT-proBNP、cTnT、MMP-9水平均低于对照组(P<0.05)。治疗前两组TLR-4、NF-κB的mRNA和蛋白表达水平无统计学差异(P>0.05)。与治疗前相比,两组治疗后TLR-4、NF-κB的mRNA和蛋白表达水平均下降(P<0.05),且治疗后实验组TLR-4、NF-κB的mRNA和蛋白表达水平均低于对照组(P<0.05)。实验组总有效率高于对照组(P<0.05);两组间不良反应发生率比较无统计学差异(P>0.05)。结论伊伐布雷定治疗慢性心力衰竭可降低患者外周血TLR-4及NF-κB的表达,同时有效改善其心功能,降低其血清炎症因子水平,可作为治疗慢性心力衰竭的有效药物。

Objective To investigate the influence of ivabradine on expressions of peripheral blood mononuclear Toll-like receptor 4(TLR4)and nuclear factor-κB(NF-κB)in patients with chronic heart failure(CHF).Methods CHF patients(n=120)were chosen and divided,according to random digital table,into control group and test group(each n=60)in Department of Cardiology in the Third People’s Hospital of Chengdu City from Jan.2020 to Jan.2023.The control group were treated with metoprolol on the base of routine therapy,and test group was treated additionally with ivabradine for 3 months.The indexes of heart function,including left ventricular ejection fraction(LVEF),left ventricular end-systolic diameter(LVESD),left ventricular diastolic diameter(LVDD),6-minute walk distance(6MWD),and serum inflammatory factors including N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin T(cTnT)and matrix metalloproteinase-9(MMP-9),and mRNA expressions of TLR-4 and NF-κB were compared between 2 groups before and after treatment.The clinical curative effect and incidence rates of adverse reactions were compared between 2 groups.Results There were no statistical differences in clinical indexes between 2 groups before treatment(P>0.05).After treatment,LVEF and 6MWD increased in 2 groups(P<0.05),and were higher in test group than those in control group(P<0.05).After treatment,LVESD and LVEDD decreased in 2 groups(P<0.05),and were lower in test group than those in control group(P<0.05).There were no statistical differences in serum inflammatory factors between 2 groups before treatment(P>0.05).After treatment,NT-proBNP,cTnT and MMP-9 decreased in 2 groups(P<0.05),and were lower in test group than those in control group(P<0.05).There were no statistical differences in mRNA and protein expressions of TLR-4 and NF-κB between 2 groups before treatment(P>0.05).After treatment,mRNA and protein expressions of TLR-4 and NF-κB decreased in 2 groups(P<0.05),and were lower in test group than those in control group(P<0.05).The total effective rate was higher in test group than that in control group(P<0.05),and incidence rates of adverse reactions had no statistical difference between 2 groups(P>0.05).Conclusion Ivabradine can reduce expressions of TLR-4 and NF-κB,effectively improve heart function,decease level of serum inflammatory factors in treatment of CHF,which is an effective medicine for CHF.