ITPR1基因对斑马鱼心脏功能的影响

发布时间：2018-06-16 20:25

本文选题：房颤 + ITPR1　；参考：《华中科技大学》2016年硕士论文

【摘要】：心房颤动是一种心律失常的现象。随着各种风险因素的增加(如年龄、肥胖、高血压),房颤的患病率会随着时间的增加而上升,并导致大量的发病率和死亡率,特别是增加了高血压与中风的风险。造成房颤的原因除了传统的各种危险因素之外,遗传因素也被证明有助于房颤的发生。心房颤动发生机制主要分为电重构和结构重构,其中电重构主要是指Na~+、K~+和Ca~(2+)等离子的循环异常。房颤的发生具有实质性的遗传基础,被认为是常染色体显性遗传。RyR2基因突变与应力诱发的多种形式的室性心动过速及心律失常性右心室发育不良有关。ITPR1基因编码1,4,5-三磷酸肌醇受体是一种配体门控离子通道蛋白,和RyR2受体一样介导钙从内质网中释放。推测ITPR1基因的下调必然会引起1,4,5-三磷酸肌醇受体的减少,影响钙离子的运输最终导致心房颤动的发生。为了探究ITPR1基因在斑马鱼心脏发育中的作用,我们首先运用整体原位杂交实验技术研究ITPR1基因在斑马鱼中各个时期表达情况,结果显示该基因存在于胚胎发育的各个时期。运用阻断基因功能的工具Morpholino(MO),通过原位杂交实验观察心脏表型变化,结果显示驻留在前侧板中胚层gata4表达区域的心脏前体细胞减弱或消失,而48 h ITPR1a的下调会造成斑马鱼心脏环化异常,推测ITPR1a基因在胚胎发育的早期对心脏的发育起着重要的作用。通过对斑马鱼的心率进行统计,发现ITPR1下调会导致斑马鱼的心率的上调,最后荧光定量PCR反应确定了ITPR1对离子通道相关基因scn5a、hcn4、cav1.3和knj2基因的调控作用。这些结果都表明了ITPR1a基因在斑马鱼心脏发育过程中起到了重要的作用。本实验研究了ITPR1a基因对斑马鱼心脏发育的影响,对于了解房颤的具体发生机制具有重要的作用,为以后房颤疾病的治疗提供了一定研究基础。
[Abstract]:Atrial fibrillation is a phenomenon of arrhythmia. With the increase of various risk factors (such as age, obesity, hypertension), the prevalence of atrial fibrillation increases with time, leading to a large number of morbidity and mortality, especially increased risk of hypertension and stroke. The cause of atrial fibrillation is due to a variety of traditional risk factors. Besides, genetic factors have also been proved to contribute to the occurrence of atrial fibrillation. The mechanism of atrial fibrillation is mainly divided into electrical and structural remodeling. Electrical remodeling mainly refers to the abnormal circulation of Na~+, K~+ and Ca~ (2+) plasma. The occurrence of atrial fibrillation has a substantial genetic basis, which is considered to be an autosomal dominant genetic mutation and stress induction. Multiple forms of ventricular tachycardia and arrhythmogenic right ventricular dysplasia associated with.ITPR1 gene encoding 1,4,5- three phosphoric inositol receptor is a ligand gated ion channel protein, which mediates calcium from the endoplasmic reticulum like RyR2 receptors. It is presumed that the downregulation of the ITPR1 gene is bound to cause the decrease of the inositol receptor of 1,4,5- three phosphoric acid. The transport of calcium ions eventually leads to atrial fibrillation. In order to explore the role of the ITPR1 gene in the development of zebrafish heart development, we first studied the expression of the ITPR1 gene in zebrafish by the whole in situ hybridization technique. The results showed that the gene existed at all stages of the development of the embryo. The functional tool Morpholino (MO) observed cardiac phenotype changes by in situ hybridization. The results showed that the cardiac precursor cells residing in the GATA4 expression area of the mesoderm of the anterior lateral plate weakened or disappeared, and the down regulation of 48 h ITPR1a resulted in the abnormal cyclization of the zebrafish heart, and that the ITPR1a gene played a role in the development of the heart at the early stage of embryonic development. An important role. By counting the heart rate of zebrafish, it was found that the down regulation of ITPR1 led to the up-regulation of the heart rate of zebrafish. The final fluorescence quantitative PCR reaction determined the regulation of ITPR1 on the gene SCN5A, HCN4, Cav1.3, and knj2 genes of the ion channel related genes. These results all indicate that the ITPR1a gene plays a role in the development of zebrafish heart. The effect of ITPR1a gene on the heart development of zebrafish is studied in this experiment. It is important for understanding the specific mechanism of atrial fibrillation and provides a basis for the treatment of future atrial fibrillation.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R541.75

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