本文選題：房顫 + ITPR1��； 參考：《華中科技大學》2016年碩士論文

【摘要】：心房顫動是一種心律失常的現(xiàn)象。隨著各種風險因素的增加(如年齡、肥胖、高血壓),房顫的患病率會隨著時間的增加而上升,并導致大量的發(fā)病率和死亡率,特別是增加了高血壓與中風的風險。造成房顫的原因除了傳統(tǒng)的各種危險因素之外,遺傳因素也被證明有助于房顫的發(fā)生。心房顫動發(fā)生機制主要分為電重構和結構重構,其中電重構主要是指Na~+、K~+和Ca~(2+)等離子的循環(huán)異常。房顫的發(fā)生具有實質(zhì)性的遺傳基礎,被認為是常染色體顯性遺傳。RyR2基因突變與應力誘發(fā)的多種形式的室性心動過速及心律失常性右心室發(fā)育不良有關。ITPR1基因編碼1,4,5-三磷酸肌醇受體是一種配體門控離子通道蛋白,和RyR2受體一樣介導鈣從內(nèi)質(zhì)網(wǎng)中釋放。推測ITPR1基因的下調(diào)必然會引起1,4,5-三磷酸肌醇受體的減少,影響鈣離子的運輸最終導致心房顫動的發(fā)生。為了探究ITPR1基因在斑馬魚心臟發(fā)育中的作用,我們首先運用整體原位雜交實驗技術研究ITPR1基因在斑馬魚中各個時期表達情況,結果顯示該基因存在于胚胎發(fā)育的各個時期。運用阻斷基因功能的工具Morpholino(MO),通過原位雜交實驗觀察心臟表型變化,結果顯示駐留在前側(cè)板中胚層gata4表達區(qū)域的心臟前體細胞減弱或消失,而48 h ITPR1a的下調(diào)會造成斑馬魚心臟環(huán)化異常,推測ITPR1a基因在胚胎發(fā)育的早期對心臟的發(fā)育起著重要的作用。通過對斑馬魚的心率進行統(tǒng)計,發(fā)現(xiàn)ITPR1下調(diào)會導致斑馬魚的心率的上調(diào),最后熒光定量PCR反應確定了ITPR1對離子通道相關基因scn5a、hcn4、cav1.3和knj2基因的調(diào)控作用。這些結果都表明了ITPR1a基因在斑馬魚心臟發(fā)育過程中起到了重要的作用。本實驗研究了ITPR1a基因?qū)Π唏R魚心臟發(fā)育的影響,對于了解房顫的具體發(fā)生機制具有重要的作用,為以后房顫疾病的治療提供了一定研究基礎。
[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.
【學位授予單位】：華中科技大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R541.75

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本文編號：2027996