美托洛尔对扩张型心肌病患者外周血单个核细胞炎性细胞因子表达和核转录因子κB/p65活化的影响  

Effects of metoprolol on lipopolysaccharide-induced expression of cytokines and activation of NF-κB/p65 in heart failure patients with dilated cardiomyopathy

作　　者：潘金生[1] 刘应才[2] 王耀辉[1] 张书灵[1] PAN Jinsheng LIU Yingcai WANG Yaohui ZHANG Shuling(Department of Cardiology,the First People＇s Hospital of Pingdingshan,Pingdingshan, Henan, 467000, Chin)

机构地区：[1]平顶山市第一人民医院心内一科,河南平顶山467000 [2]泸州医学院附属医院心内科

出　　处：《临床心血管病杂志》2016年第11期1142-1145,共4页Journal of Clinical Cardiology

摘　　要：目的:观察美托洛尔对扩张型心肌病(DCM)心力衰竭患者外周血单个核细胞(PBMCs)炎性细胞因子表达和核转录因子κB/p65(NF-κB/p65)活化的影响。方法:选取心功能Ⅱ、Ⅲ、Ⅳ级DCM心力衰竭患者35例,清晨采外周静脉血并分离出PBMCs,加入细胞因子刺激剂脂多糖(LPS)和不同浓度(0、2.5、5及10μmol/L)的美托洛尔,经体外培养24h,离心后提取上清液并采用放射免疫法检测细胞因子白细胞介素-1β(IL-1β)、IL-6和肿瘤坏死因子-α(TNF-α)水平,并将细胞悬液固定后采用免疫组织化学染色法,进行NF-κB染色,测定NF-κB阳性细胞率,分析二者相关性。结果:不同剂量美托洛尔对DCM患者IL-1β、IL-6、TNF-α和NF-κB/p65的水平均有抑制作用(均P<0.01);2.5、5及10μmol/L的美托洛尔组IL-1β、IL-6、TNF-α和NF-κB/p65的水平均明显低于0μmol/L组(均P<0.05);10μmol/L美托洛尔组IL-1β、IL-6、TNF-α和NF-κB/p65的水平均明显低于2.5、5μmol/L组(均P<0.05),而2.5、5μmol/L组IL-1β、IL-6、TNF-α和NF-κB/p65的水平差异无统计学意义(均P>0.05);在不同浓度美托洛尔组NF-κB/p65水平和IL-1β、IL-6、TNF-α水平均有明显正相关性(相关系数r值分别为0.592、0.528、0.486,P<0.01和P<0.05)。结论:在DCM心力衰竭患者中,美托洛尔可呈剂量依赖性抑制LPS诱导的PBMCs炎性细胞因子表达增加,可能是通过下调NF-κB/p65活化水平来实现的。这可能是其改善DCM心力衰竭患者心功能的作用机制之一。Objective：To investigate the effects of metoprolol on lipopolysaccharide（LPS）-induced expressions of cytokines and activation of NF-κB/p65 in peripheral blood mononuclear cells（PBMCs）in heart failure patients with dilated cardiomyopathy（DCM）.Method：Thirty-five DCM patients with heart function Ⅱ,Ⅲ and Ⅳ class,were selected.PBMCs in patients with DCM were isolated from 5ml peripheral venous blood,stimulated by LPS,respectively added with 0umol/l,2.5μmol/L,5μmol/L and 10μmol/L metoprolol,and cultured for 24 hours.Supernatant liquid was centrifuged.IL-1β,IL-6,and TNF-αlevels were measured by radio immunity method.NF-κB/p65 in cell suspension was measured by immunohistochemistry staining,positive rate was calculated,and its correlation with the cytokine levels was analyzed.Result：The levels of IL-1β,IL-6,TNF-α,and NF-κB/p65 were all significantly decreased（P〈0.01）in different metoprolol groups.Compared with the 0μmol metoprolol group,the levels of IL-1β,IL-6,TNF-α,and NF-κB/p65 in 2.5μmol/L,5μmol/L,and 10μmol/L metoprolol groups were significantly decreased（P〈0.05）.The levels of IL-1β,IL-6,TNF-α,and NF-κB/p65 in 10μmol/L metoprolol group were more significantly decreased than those in 2.5μmol/L or 5μmol/L group（P〈0.05）,but there were no significantly difference between 2.5μmol/L group and 5μmol/L group（P〉0.05）.There was an evidently positive relation between NF-κB/p65 and,IL-1β,IL-6,and TNF-α（r=0.592,0.528 P〈0.01;r=0.486P〈0.05）.Conclusion：Metoprolol can dose-dependently suppress the expression of the cytokines induced by LPS in PBMCs in heart failure patients with DCM.It was the possible mechanism that metoprolol decreased the cytokines levels through suppressing of the NF-κB/p65 activation.Whereby,it might be one reason for metoprolol to improve the cardiac function of heart failure in DCM patients.

关 键 词：心肌病 扩张型 细胞因子类 心力衰竭 美托洛尔 核转录因子-ΚB 

分 类 号：R542.2[医药卫生—心血管疾病]