噻唑烷二酮类胰岛素增敏药和LOX-1对心脏成纤维细胞功能的调节作用(英文)  

Modulation of cardiac fibroblast function by thiazolidinediones with a focus on the role of LOX-1

作　　者：陈家伟[1,2] 胡长平[1,3] Jawahar L.Mehta 

机构地区：[1]Gene Therapy Program,Division of Cardiovascular Medicine,University of Arkansas for Medical Sciences and VA Medical Center,AR 72205,USA [2]复旦大学附属肿瘤医院麻醉科 [3]中南大学药学院药理学系

出　　处：《中南大学学报（医学版）》2011年第10期939-948,共10页Journal of Central South University ：Medical Science

基　　金：supported by Specialized Research Fund for the Doctoral Program of Higher Education,Ministry of Education of China(20100162110058 to CPH);the Department of Veterans Affairs,Washington,DC,USA(JLM)and the Arkansas Bioventures Institute,Little Rock,AR,USA(JLM)

摘　　要：心脏成纤维细胞在心脏重构中起重要作用。在各种促纤维化因素(如前炎症因子、缺氧-复氧、压力超负荷、衰老)刺激下,心脏成纤维细胞增殖、迁移、激活,导致细胞基质成分的积聚、心脏肥厚和僵硬。过氧化物酶增殖体激活受体γ(PPAR-γ)的配体,特别是噻唑烷二酮类胰岛素增敏药,在病理条件下可调节心脏成纤维细胞的功能以及心脏重构的发展,然而未发现噻唑烷二酮类胰岛素增敏药对心脏衰竭的有益作用。噻唑烷二酮类胰岛素增敏药调节心脏成纤维细胞功能和心脏重构的确切信号通路未完全阐明,现有证据提示涉及氧化应激及相关信号途径。此外,PPAR-γ和植物凝集素样氧化型低密度脂蛋白受体-1(LOX-1)在其中起重要作用。Cardiac fibroblasts play a pivotal role in cardiac remodeling.In response to various pro-fibrotic stimuli,such as pro-inflammatory cytokines,anoxia-reoxygenation and pressure overload as well as aging,cardiac fibroblasts undergo proliferation,migration and activation,leading to the accumulation of extracellular matrix components and increased thickness and stiffness of heart.The ligands for peroxisome proliferator-activated receptor γ,especially thiazolidinediones,modulate the function of cardiac fibroblasts and the progression of cardiac remodeling,especially under pathological conditions.Unfortunately these agents have not been found to be consistently beneficial in heart failure.Although the precise intracellular signaling pathways are not fully understood,existing evidence strongly supports the involvement of oxidative stress and related signaling pathways.Further,peroxisome proliferator-activated receptor γ and lectin-like oxidized low-density lipoprotein receptor-1 together play critical roles in thiazolidinediones-modulated cardiac fibroblast dysfunction.

关 键 词：心脏成纤维细胞 噻唑烷二酮类胰岛素增敏药 植物凝集素样氧化型低密度脂蛋白受体-1 过氧化物酶增殖体激活受体Γ 

分 类 号：R965[医药卫生—药理学]