cFLIP在压力超负荷诱导的心肌肥厚及纤维化中的作用  

The role of cFLIP in cardiac hypertrophy and fibrosis induced by chronic pressure overload

作　　者：王纯奕[1] 范阳[1] 汪心安[1] 肖金凤[1] 黎明江[1] 李红良[1] 夏豪[1] 

机构地区：[1]武汉大学人民医院心内科武汉大学心血管病研究所,湖北武汉430060

出　　处：《中国心脏起搏与心电生理杂志》2012年第2期152-155,共4页Chinese Journal of Cardiac Pacing and Electrophysiology

摘　　要：目的利用基因工程小鼠研究细胞型Fas相关死亡区域蛋白样β白介素-1转换酶抑制蛋白基因(cFLIP)在压力超负荷诱导的心肌肥厚及心肌纤维化中的作用。方法 cFLIP杂合子小鼠(heterozygote,HZ)和cFLIP野生型小鼠(wild type,WT)各20只分别随机分为模型组和假手术组,每组10只。主动脉缩窄术建立小鼠心肌肥厚模型,术后4周超声检测小鼠心室腔大小及左室短轴缩短率,组织病理学方法评价心肌肥厚及纤维化程度,实时定量聚合酶链式反应在mRNA水平检测心肌肥厚标志物心钠肽,脑钠肽,β-MHC以及心肌纤维化标志物结缔组织生长因子(CTGF),Ⅰ、Ⅳ型胶原(collagenⅠ,Ⅳ),TGF-β1。结果术后4周,HZ模型组较WT模型组和HZ假手术组心室腔增大,左室短轴缩短率下降(P<0.05,n=10);心肌肥厚及纤维化组织病理学检测及相关标志物表达水平模型组较假手术组升高(P<0.05,n=10),而HZ模型组表达增加程度较WT模型组更为显著(P<0.05,n=10)。结论cFLIP可抑制心肌肥厚及纤维化,对心功能起保护作用。Objective To clarify the role of cellular Fas-associated death domain-like interleukin-1β-converting enzyme（FLICE）-like inhibitory protein（cFLIP）gene in cardiac hypertrophy and fibrosis induced by chronic pressure overload.Methods Twenty cFLIP heterozygote（HZ）mice and twenty wild-type cFLIP（WT）mice were randomly divided into model group and sham group equtionally（n=10）.Cardiac hypertrophy model was established through aortic banding surgery.Four weeks after the aortic banding operation,cardiac function were evaluated by ultrasonic diagnosis equipment,and the degree of cardiac hypertrophy and fibrosis were evaluated by histological detection.In addition,the markers of cardiac hypertrophy including brain natriuretic peptide,atrial natriuretic peptide,and β-myosin heavy chain（β-MHC）,fibrosis markers connective tissue growth factor（CTGF）,transforming growth factor-β1（TGF-β1）,and collagen Ⅰ,Ⅳ were detected by real-time quantitative polymerase chain reaction（PCR）at the mRNA level.Results Four weeks after the aortic banding operation,the physiological parameters and analysis of cardiac size and function of HZ group were reduced significantly（P0.05,n=10）,and the degree of cardiac hypertrophy and fibrosis were increased dramatically（P0.05,n=10） while compared with those of WT group.Conclusion The cFLIP protects against the development of cardiac hypertrophy and fibrosis.

关 键 词：心血管病学 CFLIP 基因敲除 心肌肥厚 纤维化 心功能 

分 类 号：R331.31[医药卫生—人体生理学]