核因子-kB参与压力负荷性心力衰竭的发病机制研究  

Nuclear factor-κB is required for pressure overload-induced heart failure

作　　者：王永梅[1] 李婷[1] 胡玉龙[1] 李菁[1] 陈亮[2] 李跃华[1] 

机构地区：[1]南京医科大学病理生理学系,江苏南京210029 [2]南京医科大学第一附属医院心胸外科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2007年第8期777-780,784,F0002,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(30571842);南京医科大学科技创新基金(CX2004001)

摘　　要：目的:研究核因子-kB(NF-kB)在心脏压力负荷增加所诱导的心力衰竭的发病过程中的相关改变。方法:SD大鼠采用主动脉弓部缩窄术,术后12周对大鼠进行心功能分析;采用心肌组织Masson染色评估术后纤维化程度:凝胶迁移率电泳(electrophoretic mobility shift assay,EMSA)方法检测心肌组织中NF-kB结合活性改变:并利用免疫共沉淀方法(immunoprecipitation,IP)对上游信号分子Toll-like receptor4(TLR4)与myeloid differentiation primary-response protem 8(MyD88)的相互结合作用进行分析。结果:SD大鼠术后12周心脏收缩及舒张功能与假手术组相比较均有明显下降,其心肌组织纤维化程度明显加重。NF-kB在肥大心肌组织中的结合活性与周龄适配的假手术组相比显著增加(P<0.05),其上游两个重要的信号分子TLR4/ MyD88的相互结合作用增强(P<0.05)。结论:NF-kB参与了压力负荷增加诱导的心力衰竭的发病过程的调控。Objective：To study nuclear factor-κB（NF-κB）activation in heart failure due to chronic pressure-overload.Methods：SD rats were performed by transverse aortic banding for 12 weeks.After that hemodynamic parameters and cardiac fibrosis were measured; NF-κB binding activity was analyzed by electrophoretic mobility shift assay（EMSA）;Immunoprecipitation（IP）was performed to analysis Toll-like receptor 4（TLR4）and myeloid differentiation primary-response protein 8（MyD88）association.Results：Both systolic and diastolic function were significantly reduced compared with sham operated group（P〈0.05）,and cardiac fibrosis enhanced predominantly.NF-κB binding activity in hypertrophic heart tissue was higher than that of sham operated group（P〈0.05）as well as TLR4/MyD88 association（P〈0.05）.Conclusion： NF-κB was required for chronic pressure overload-induced heart failure.

关 键 词：心力衰竭 信号转导 核因子-KB 

分 类 号：R743.31[医药卫生—神经病学与精神病学] Q74[医药卫生—临床医学]