扩张型心肌病患者合并恶病质后TLR4/JNK MAPK信号转导通路的变化  

The changes of TLR4/JNK MAPK signal transduction pathway in dilated cardiomyopathy patients with cachexia

作　　者：赵欣[1] 张昕[2] 

机构地区：[1]包头医学院第一附属医院包头医学院2013级研究生,内蒙古包头014010 [2]包头医学院第一附属医院心功能科,内蒙古包头014010

出　　处：《临床心血管病杂志》2016年第6期614-618,共5页Journal of Clinical Cardiology

摘　　要：目的：探讨TOLL样受体4/c-Jun氨基末端激酶、丝裂原活化蛋白激酶信号转导通路（TLR4/JNK MAPK信号转导通路）是否参与扩张型心肌病（扩心病）后恶病质的发生。方法：入选2013-2015年就诊于包头医学院第一附属医院,确诊为扩张型心肌病,心功能Ⅱ-Ⅳ级（NYHA分级）患者60例。根据6个月体重下降是否〉6%分为心力衰竭（心衰）恶病质（cCHF）组（36例）和心衰非恶病质（ncCHF）组（24例）。另入选年龄、性别匹配的健康体检者24例为对照组。于入院第2天清晨,采集空腹静脉血2ml,离心后取上层血清,酶联免疫吸附法（ELISA法）测肿瘤坏死因子（TNF）-α、白细胞介素（IL）1、IL-6浓度及TLR4和JNK蛋白含量;另于入院第2天清晨采集恶病质患者静脉血4ml,分离单个核细胞并培养4h,根据是否在培养基中加入JNK特异性抑制剂SP600125分为抑制剂组和无抑制剂组,后者加入等剂量的二甲基亚砜,实时定量PCR法测两组TNF-α、IL-1、IL-6mRNA的相对表达量。结果：1TNF-α、IL-1和IL-6浓度：cCHF组显著高于ncCHF组和对照组（P〈0.05）,且ncCHF组高于对照组（P〈0.05）。2TLR4和JNK蛋白含量：cCHF组显著高于ncCHF组和对照组（P〈0.05）,且ncCHF组高于对照组（P〈0.05）。3TNF-α、IL-1、IL-6 mRNA的相对表达量：抑制剂组TNF-α、IL-1、IL-6mRNA的相对表达量较无抑制剂组降低（P〈0.05）。结论：扩心病合并恶病质患者体内TNF-α、IL-1和IL-6浓度升高,TLR4/JNK MAPK信号转导通路可通过影响TNF-α、IL-1和IL-6的转录来参与心衰恶病质的发生。Objective：To explore whether the Toll like receptor 4/c-Jun N terminal kinase mitogen-activated protein kinase signal transduction pathway was related to the occurrence of cardiac cachexia.Method：Sixty patients with dilated cardiomyopathy who were in New York Heart Association functional class II to IV were selected in the First Affiliated Hospital of Baotou Medical College in 2013-2015.The patients were divided into cardiac cachexia group,heart failure non cachexia group and control group,according to whether the weight loss within 6months was greater than 6%.The control group included 24 cases of age-and sex-matched healthy subjects.The next day morning of admission to the hospital,2ml peripheral blood were collected and centrifuged,the serum were used to detect the tumor necrosis factor（TNF）alpha,interleukin 1（IL-1）,interleukin 6（IL-6）concentration and TLR4 and JNK protein content by enzyme-linked immune adsorption assay（ELISA）.Another 4ml peripheral blood of patients with cachexia were gathered to obtain Peripheral-blood mononuclear cells and then cultured for 4hours.According to whether the JNK specific inhibitor（SP600125）was added to the culture medium,they were divided into two groups,the inhibitor group and the non inhibitor group,and isodose dimethyl sulfoxide was added to the letter.The mRNA expression of TNF-α,IL-1,IL-6of the two groups were examined by realtime polymerase chain reation.Result：The levels of TNF-α,IL-1and IL-6in cardiac cachexia group were significantly higher than those in heart failure non cachexia group（P〈0.05）and control group（P〈0.05）,and the heart failure non cachexia group were higher than the control group（P〈0.05）.The protein content of TLR4 and JNK in cardiac cachexia group were significantly higher than those in heart failure non cachexia group（P〈0.05）and control group（P〈0.05）,and the heart failure non cachexia group were higher than the control group（P〈0.05）.The mRNA expression of TNF-α,IL-1,IL-6in the inhibitor

关 键 词：心力衰竭 恶病质 TOLL样受体 丝裂原活化蛋白激酶 信号转导通路 

分 类 号：R541.6[医药卫生—心血管疾病]