大鼠心肌梗塞后心室重构中miRNA的差异表达

Differential Expression of miRNA in Ventricular Remodeling after Myocardial Infarction in Rats

目的:筛选大鼠急性心梗后的心室重构过程中差异表达的微小RNA(microRNA,miRNA),为miRNA调控心室重构的机制研究提供靶标。方法:20只成年雄性Wistar大鼠,分组如下:心肌梗死组(MI组,n=10)和假手术组(Sham组,n=10)。通过结扎大鼠左冠状动脉前降支构建急性心梗模型建模。4周后对大鼠进行超声心动图检查和梗死边缘区心肌HE染色观察心室重构程度。利用miRNA芯片对心梗边缘区的miRNA进行差异表达检测,采用实时定量PCR验证芯片结果的可靠性。结果:心脏超声显示MI组大鼠左室重构明显,心梗边缘区心肌HE染色可见细胞间质大量胶原纤维沉积。miRNA芯片结果显示15个miRNA在心梗4周后呈差异表达,其中11个miRNA(miR-21、miR-23a、miR-125b、miR-132、miR-146b、miR-181b、miR-199a、miR-320、miR-324、miR-328和miR-499)表达上调,4个miRNA(miR-29、miR-30c、miR-133a和miR-208)表达下调。实时定量PCR验证结果与芯片结果一致。结论:这些差异表达的miRNA可能与心梗后心室重构相关,进一步深入研究特定miRNA的调控机制有望为基因治疗提供新靶点。

Objective：To screen the miRNA differential expression profile in ventricular remodeling after myocardial infarction in rats and identify the target of miRNA in the mechanism of ventricular remodeling.Methods：A total of 20 male Wistar rats were randomly assigned into MI group（n=10） and Sham group（n=10）.MI rats were induced by ligation of the anterior descending coronary artery.Four weeks later,ventricular remodeling were measured by echocardiography and HE staining.The miRNA in the cardiac tissues of border zone were measured by miRNA microarray.The miRNA that expressed significantly differently would be verified by Real time quantitative PCR.Results：Echocardiographic results showed serious ventricular remodeling in the MI rats.HE staining revealed significant collagen deposition around the border area of the infarct region.By significance analysis of microarray based on microarray screening,15 significantly different expression of miRNA were obtained after myocardial infarction for 4 weeks.11 miRNA were significantly up-regulated（miR-21,miR-23a,miR-125b,miR-132,miR-146b,miR-181b,miR-199a,miR-320,miR-324,miR-328 and miR-499） and 4 miRNA were significantly down-regulated（miR-29,miR-30c,miR-133a and miR-208）.Real time quantitative PCR approved the results as well.Conclusions：These significantly differently expressed miRNA might be related with ventricular remodeling after myocardial infarction and further studies of the mechanism of some specific miRNA would be a new target of gene therapy.