本文選題：冠脈旁路移植術(shù) + 術(shù)后房顫��； 參考：《北京協(xié)和醫(yī)學(xué)院》2015年博士論文

【摘要】：背景：房顫(Atrial Fibrillation, AF)是一種常見的心律失常,其發(fā)病率在全球范圍內(nèi)呈逐漸增高之勢,嚴(yán)重地影響著人類的健康和生命,也給社會帶來了相當(dāng)大的經(jīng)濟(jì)負(fù)擔(dān),因此受到普遍關(guān)注。大量研究表明房顫是一種進(jìn)行性疾病,開始為陣發(fā)性,可自行中止,然后多轉(zhuǎn)變?yōu)槌掷m(xù)性,只有用藥物或電復(fù)律才可以轉(zhuǎn)為竇性心律,最后部分發(fā)展為永久性心房顫動,藥物和電復(fù)律效果不佳,且復(fù)律后易復(fù)發(fā)。目前雖然對AF的了解日益加深,但其發(fā)病、進(jìn)展以及其與相關(guān)疾病之間的關(guān)聯(lián),尚未完全了解。術(shù)后房顫(postoperative atrial fibrillation,POAF)是冠脈旁路移植術(shù)(CABG)最常見的并發(fā)癥之一,迄今為止其發(fā)生的病理生理機(jī)制尚未闡明。肌纖維能量學(xué)的改變可能促成心房收縮障礙,糖酵解酶在持續(xù)性房顫時代償性的上調(diào),而且代謝改變的不一致在術(shù)后房顫的易感人群中也得到證實,提示能量代謝異常與房顫的發(fā)生存在相關(guān)性。過氧化物酶體增殖物激活受體Y協(xié)同刺激因子1α(peroxisome proliferator activated receptor y coactivator 1α, PGC-1α)是近年來倍受關(guān)注的輔激活因子。研究表明,PGC-1α參與適應(yīng)性產(chǎn)熱調(diào)節(jié)、肝糖異生、脂肪酸p氧化等代謝調(diào)節(jié),是調(diào)節(jié)線粒體氧化代謝的主要調(diào)控因子。在心臟中激活PGC-1 α調(diào)控的級聯(lián)反應(yīng)能夠增加心肌線粒體的氧化能力。Fuentes E等人研究認(rèn)為PGC-1α及其共活化因子是治療代謝性疾病和相關(guān)心血管疾病的良好靶點。目前關(guān)于PGC-1α與心肌能量代謝代謝紊亂的關(guān)系尚未明確,缺少相關(guān)作用機(jī)制的研究。葡萄糖在局部缺血心肌的能量生成中居于核心地位。葡萄糖轉(zhuǎn)運體家族(GLUTs)是心肌攝取葡萄糖的主要轉(zhuǎn)運蛋白,現(xiàn)已在心肌中發(fā)現(xiàn)有GLUT1、GLUT3和GLUT4三種亞型,經(jīng)由GLUT1轉(zhuǎn)運的葡萄糖是細(xì)胞內(nèi)的基本組成成分,而GLUT4介導(dǎo)的是誘導(dǎo)吸收的葡萄糖。三種亞型中GLUT3轉(zhuǎn)運效能最高。目前關(guān)于GLUTs與心肌缺血再灌注后葡萄糖的攝取、氧化及房顫發(fā)生的研究尚處于空白狀態(tài),有必要深入研究相關(guān)機(jī)制。目的：探討冠心病患者心肌內(nèi)PGC-1α及GLUT3的蛋白表達(dá)水平和相應(yīng)nRNA表達(dá)水平與線粒體功能障礙及CABG術(shù)后房顫易感性的關(guān)系。方法：入選擬行CABG術(shù)的冠心病患者,收集患者術(shù)前、術(shù)中和術(shù)后的資料。術(shù)前觀察患者心房大小、排空、CRP、血脂血糖水平、肝腎功能等生化指標(biāo),在術(shù)中開始體外循環(huán)前獲取右心耳組織超低溫保存?zhèn)浞治?術(shù)后新發(fā)房顫由持續(xù)心電監(jiān)測及心電圖評定,觀察入選患者術(shù)后新發(fā)房顫的發(fā)生,將新發(fā)房顫患者及正常心律患者分組對照,對各組患者基線資料及組織標(biāo)本中的PGC-1α及GLUT3的蛋白表達(dá)水平和相應(yīng)mRNA表達(dá)水平進(jìn)行對照比較。心肌組織勻漿后PGC-1α及GLUT3的蛋白表達(dá)水平用酶聯(lián)免疫吸附劑測定(enzyme linked immunosorbent assay, ELISA)方法測定；PGC-1α及GLUT3相應(yīng)mRNA的表達(dá)水平采用QRT-PCR方法測定。使用SPSS 13.0等軟件進(jìn)行數(shù)據(jù)清洗及數(shù)據(jù)分析,使用Excel、Access、Epiinfo等作為輔助。對數(shù)據(jù)進(jìn)行均數(shù)、中位數(shù)、標(biāo)準(zhǔn)差、頻數(shù)等描述性分析；t檢驗、秩和檢驗、單因素方差分析等單因素分析；多因素相關(guān)、logistic回歸等多因素分析。結(jié)果：共入選79例患者(男性：63人),平均年齡：59.88±8.62年,其中22例患者出現(xiàn)新發(fā)房顫。PGC-1α及GLUT3的蛋白及相應(yīng)mRNA表達(dá)水平在發(fā)生術(shù)后房顫的患者組中明顯較低,與POAF明顯相關(guān)(P0.05)。糖尿病患者中PGC-1 α的蛋白及相應(yīng)nRN A表達(dá)水平也較非糖尿病患者偏低(P0.05)。在多元線性回歸模型中,低PGC-1α水平與年齡、糖尿病史、總膽固醇明顯相關(guān)(P0.05)。結(jié)論：心房肌能量代謝的不良調(diào)節(jié)以及葡萄糖攝取能力的不足先于術(shù)后房顫的發(fā)生,心房肌組織能量代謝發(fā)生障礙的患者發(fā)生術(shù)后房顫的風(fēng)險明顯增高而且調(diào)節(jié)心房肌能量代謝的PGC-1α的蛋白及mRNA表達(dá)水平減低與糖尿病明顯相關(guān)。我們的研究提示,心房肌組織能量代謝障礙是導(dǎo)致CABG術(shù)后房顫的可能機(jī)制。
[Abstract]:Background: Atrial Fibrillation (AF) is a common arrhythmia. Its incidence is increasing around the world. It seriously affects human health and life, and it also brings considerable economic burden to society. Therefore, the large amount of research shows that atrial fibrillation is an progressive disease and is started as an array. It can be stopped by itself and then to be more persistent. Only by drug or electric cardioversion can it be converted into sinus rhythm, and the final part is permanent atrial fibrillation. The effects of drug and electric cardioversion are poor and relapse after cardioversion. Although the understanding of AF is deepening, its incidence, progress, and its association with related diseases are present. Postoperative atrial fibrillation (POAF) is one of the most common complications of coronary artery bypass grafting (CABG). To date, the pathophysiological mechanism has not been elucidated. The changes in muscle fiber energy may contribute to atrial contraction obstruction, and glycolytic enzymes are up-regulated in the period of persistent atrial fibrillation. The inconsistency of metabolic changes is also confirmed in the susceptible population of postoperative atrial fibrillation, suggesting that there is a correlation between abnormal energy metabolism and the occurrence of atrial fibrillation. The peroxisome proliferator activated receptor Y (peroxisome proliferator activated receptor y coactivator 1 alpha, PGC-1 a) is a supplementary irritation in recent years. The study shows that PGC-1 alpha participates in the regulation of adaptive heat production, liver sugar isogenesis, and fatty acid P oxidation, which is the main regulator of mitochondrial oxidative metabolism. The cascade of PGC-1 alpha regulated in the heart can increase the oxidative capacity of myocardial mitochondria,.Fuentes E et al. Studies believe that PGC-1 alpha and its CO activation cause are considered. It is a good target for the treatment of metabolic diseases and related cardiovascular diseases. The relationship between PGC-1 alpha and the metabolic disorder of myocardial energy metabolism is not clear, and the study of the mechanism is lacking. Glucose is at the core of the energy generation of ischemic myocardium. The glucose transporter family (GLUTs) is the glucose uptake of glucose in the myocardium The main transporter protein, three subtypes of GLUT1, GLUT3 and GLUT4, has been found in the myocardium. Glucose transported by GLUT1 is the basic component of the cell, and GLUT4 is mediated by the induced absorption of glucose. The highest GLUT3 transport efficiency in the three subtypes is the glucose uptake and oxidation of GLUTs and myocardial ischemia and reperfusion. Research on the occurrence of atrial fibrillation is still in a blank state, and it is necessary to study the related mechanisms. Objective: To explore the relationship between the protein expression level of PGC-1 alpha and GLUT3 and the corresponding nRNA expression level with the mitochondrial dysfunction and the susceptibility to atrial fibrillation after CABG. Methods: to collect the patients with coronary heart disease and collect the patients with CABG. Preoperative, intraoperative and postoperative data. Preoperative observation of the patient's atrial size, emptying, CRP, blood lipid and blood glucose levels, liver and kidney function and other biochemical indicators, before the operation started extracorporeal circulation to obtain the right auricle tissue cryopreservation analysis, after the operation of the new atrial fibrillation by continuous ECG monitoring and electrocardiogram assessment, observe the patients after the operation of the new atrial fibrillation after the operation. A comparison of the levels of PGC-1 alpha and GLUT3 protein expression and the corresponding mRNA expression levels in the baseline data and tissue specimens of the patients were compared. The protein expression levels of PGC-1 alpha and GLUT3 were measured by enzyme linked immunosorbent (enzyme linked immunos) after the homogenate of myocardial tissue. Orbent assay, ELISA) method determination; PGC-1 alpha and GLUT3 corresponding mRNA expression level by QRT-PCR method. Use SPSS 13 software to carry out data cleaning and data analysis, using Excel, Access, Epiinfo and other descriptive analysis of data, median, standard deviation, frequency and other descriptive analysis; t test, rank sum test, Dan Yin Multiple factor analysis, such as plain variance analysis, multiple factor correlation and logistic regression. Results: a total of 79 patients (male: 63 people), average age: 59.88 + 8.62 years, of which 22 cases of new atrial fibrillation.PGC-1 alpha and GLUT3 protein and corresponding mRNA expression in patients with postoperative atrial fibrillation were significantly lower, and P OAF was significantly correlated (P0.05). The protein and corresponding nRN A expression level of PGC-1 alpha in diabetic patients was also lower than that of non diabetic patients (P0.05). In multiple linear regression model, the low PGC-1 alpha level was significantly associated with age, diabetes history and total cholesterol (P0.05). Conclusion: the poor regulation of energy metabolism and glucose uptake ability of the atrial myosin muscle (P0.05). The risk of atrial fibrillation in patients with atrial tissue energy metabolism is significantly higher than that of postoperative atrial fibrillation. The decrease of PGC-1 alpha protein and mRNA expression level in atrial muscle energy metabolism is significantly associated with diabetes. Our study suggests that the energy metabolism disorder in atrial muscle is the cause of CABG after operation. The possible mechanism of atrial fibrillation.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R541.75

【共引文獻(xiàn)】

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10 李s，

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