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

【摘要】：心房顫動(dòng)是一種心律失常的現(xiàn)象。隨著各種風(fēng)險(xiǎn)因素的增加(如年齡、肥胖、高血壓),房顫的患病率會(huì)隨著時(shí)間的增加而上升,并導(dǎo)致大量的發(fā)病率和死亡率,特別是增加了高血壓與中風(fēng)的風(fēng)險(xiǎn)。造成房顫的原因除了傳統(tǒng)的各種危險(xiǎn)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(dòng)發(fā)生機(jī)制主要分為電重構(gòu)和結(jié)構(gòu)重構(gòu),其中電重構(gòu)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(shí)質(zhì)性的遺傳基礎(chǔ),被認(rèn)為是常染色體顯性遺傳。RyR2基因突變與應(yīng)力誘發(fā)的多種形式的室性心動(dòng)過速及心律失常性右心室發(fā)育不良有關(guān)。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(dǎo)鈣從內(nèi)質(zhì)網(wǎng)中釋放。推測(cè)ITPR1基因的下調(diào)必然會(huì)引起1,4,5-三磷酸肌醇受體的減少,影響鈣離子的運(yùn)輸最終導(dǎo)致心房顫動(dòng)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(yùn)用整體原位雜交實(shí)驗(yàn)技術(shù)研究ITPR1基因在斑馬魚中各個(gè)時(shí)期表達(dá)情況,結(jié)果顯示該基因存在于胚胎發(fā)育的各個(gè)時(shí)期。運(yùn)用阻斷基因功能的工具M(jìn)orpholino(MO),通過原位雜交實(shí)驗(yàn)觀察心臟表型變化,結(jié)果顯示駐留在前側(cè)板中胚層gata4表達(dá)區(qū)域的心臟前體細(xì)胞減弱或消失,而48 h ITPR1a的下調(diào)會(huì)造成斑馬魚心臟環(huán)化異常,推測(cè)ITPR1a基因在胚胎發(fā)育的早期對(duì)心臟的發(fā)育起著重要的作用。通過對(duì)斑馬魚的心率進(jìn)行統(tǒng)計(jì),發(fā)現(xiàn)ITPR1下調(diào)會(huì)導(dǎo)致斑馬魚的心率的上調(diào),最后熒光定量PCR反應(yīng)確定了ITPR1對(duì)離子通道相關(guān)基因scn5a、hcn4、cav1.3和knj2基因的調(diào)控作用。這些結(jié)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(shí)驗(yàn)研究了ITPR1a基因?qū)Π唏R魚心臟發(fā)育的影響,對(duì)于了解房顫的具體發(fā)生機(jī)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(chǔ)。
[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(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R541.75

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本文編號(hào)：2027996