增龄和心房颤动所致的左心房结构重构与miRNA表达改变的相关性研究

Structural remodeling of left atrial induced by aging and atrial fibrillation involved in the changes in miRNAs expression

目的：探讨增龄和心房颤动（房颤）所致的左心房结构重构是否与miRNAs的表达改变相关。方法由新疆医科大学第一附属医院动物实验中心提供的21只犬分为3组：成年窦性心律组、老年窦性心律组和老年持续性房颤组。通过持续快速心房起搏建立房颤模型,用实时荧光定量聚合酶链反应（ qRT-PCR）的方法检测3组犬左心房心肌细胞miRNA-1、miRNA-21、miRNA-29和miRNA-133的表达变化；应用光镜、电镜检测各组左心房心肌病理组织学和超微结构的改变。 DNA断裂的原位末端标记法（ TUNEL）检测细胞凋亡指数。结果在窦性心律时,与成年组相比较,老年组左心房心肌细胞miRNA-21,miRNA-29的表达水平呈现显著上调趋势（miRNA-21,2．3671±0．3056对1．3529±0．1921；miRNA-29,2．1929±0．2726对1．2430±0．1828,P〈0．05）；miRNA-1,miRNA-133的表达水平呈现出显著下调趋势（miRNA-1,0．7518±0．1009对1．2036±0．1328；miRNA-133,1．0438±0．1282对1．2705±0．2025, P〈0．05）；与窦性心律老年组相比较,持续性房颤老年组左心房心肌细胞miRNA-1、miRNA-21、miRNA-29的表达水平显现出显著上调趋势（ miRNA-1,1．2475±0．2091对0．7518±0．1009；miRNA-21,3．8251±0．316对2．367±0．3056；miRNA-29；3．4532±0．3076对2．1929±0．2726,P〈0．05）；miRNA-133的表达水平显现显著下调趋势（miRNA-133,0．7439＋0．1026对1．0438＋0．1292,P〈0．05）。伴随增龄与房颤,犬心肌纤维化程度、细胞超微结构及凋亡指数差异有统计学意义（P〈0．05）。结论伴随增龄与房颤而显现的miRNA-1、miRNA-21、miRNA-29和miRNA-133的表达改变与病理性心房重构相关。

Objective The study was designed to decipher whether the structure remodeling of left at-rial induced by aging and atrial fibrillation （ AF ） correlated with changes in miRNAs expres-sion. Methods Dogs were divided into 3 groups randomly：adult and old groups in sinus rhythm （ SR） and old group with chronic AF. AF model was induced by rapid atrial pacing. Expressions of miRNA-1,miRNA-21, miRNA-29 and miRNA-133 were measured by Quantitative Real-Time Polymerase Chain Reaction （ qRT-PCR） . Pathohistological and ultrastructural changes were analyzed by light and electron microscopy. Apoptosis index of myocytes was detected by TdT-mediated dUTP nick end labeling（ TUNEL） . Results In sinus rhythm group,compared to the adult group,the expressions of miRNA-21,29 were significantly increased（ miRNA-21, 2. 3671±0. 3056 vs. 1. 3529±0. 1921;miRNA-29,2. 1929±0. 2726 vs. 1. 2430±0. 1828,P〈0. 05）,whereas the expressions of miRNA-1,miRNA-133 showed obviously down-regulation tendencye in the aged group（miRNA-1, 0. 7518±0. 1009 vs. 1. 2036±0. 1328;miRNA-133,1. 0438±0. 1282 vs. 1. 2705±0. 2025,P〈0. 05）. Compared to the aged group in sinus rhythm,the expressions of miRNA-1,miRNA-21,miRNA-29 were significantly in-creased in the old group in AF（miRNA-1,1. 2475±0. 2091 vs. 0. 7518±0. 1009;miRNA-21,3. 8251±0. 316 vs.＆amp;nbsp;2. 3671±0. 3056;miRNA-29;3. 4532±0. 3076 vs. 2. 1929±0. 2726,P〈0. 05）. In contrast,the expressions of miRNA-133 showed obviously down-regulation tendency（miRNA-133,0. 7439＋0. 1026 vs. 1. 0438＋0. 1292,P〈0. 05）. Samples of atrial tissue showed statistical significance changes（all P〈0. 05）in fibrosis degree,ultra-structural and apoptosis index with aging and/or in AF dogs. Conclusion These changes in miRNAs expres-sion may be responsible for pathological atrialremodeling with aging and AF.