心脏能量代谢障碍与CABG术后房颤易感性的研究

发布时间：2018-05-14 18:33

本文选题：冠脉旁路移植术 + 术后房颤　；参考：《北京协和医学院》2015年博士论文

【摘要】：背景：房颤(Atrial Fibrillation, AF)是一种常见的心律失常,其发病率在全球范围内呈逐渐增高之势,严重地影响着人类的健康和生命,也给社会带来了相当大的经济负担,因此受到普遍关注。大量研究表明房颤是一种进行性疾病,开始为阵发性,可自行中止,然后多转变为持续性,只有用药物或电复律才可以转为窦性心律,最后部分发展为永久性心房颤动,药物和电复律效果不佳,且复律后易复发。目前虽然对AF的了解日益加深,但其发病、进展以及其与相关疾病之间的关联,尚未完全了解。术后房颤(postoperative atrial fibrillation,POAF)是冠脉旁路移植术(CABG)最常见的并发症之一,迄今为止其发生的病理生理机制尚未阐明。肌纤维能量学的改变可能促成心房收缩障碍,糖酵解酶在持续性房颤时代偿性的上调,而且代谢改变的不一致在术后房颤的易感人群中也得到证实,提示能量代谢异常与房颤的发生存在相关性。过氧化物酶体增殖物激活受体Y协同刺激因子1α(peroxisome proliferator activated receptor y coactivator 1α, PGC-1α)是近年来倍受关注的辅激活因子。研究表明,PGC-1α参与适应性产热调节、肝糖异生、脂肪酸p氧化等代谢调节,是调节线粒体氧化代谢的主要调控因子。在心脏中激活PGC-1 α调控的级联反应能够增加心肌线粒体的氧化能力。Fuentes E等人研究认为PGC-1α及其共活化因子是治疗代谢性疾病和相关心血管疾病的良好靶点。目前关于PGC-1α与心肌能量代谢代谢紊乱的关系尚未明确,缺少相关作用机制的研究。葡萄糖在局部缺血心肌的能量生成中居于核心地位。葡萄糖转运体家族(GLUTs)是心肌摄取葡萄糖的主要转运蛋白,现已在心肌中发现有GLUT1、GLUT3和GLUT4三种亚型,经由GLUT1转运的葡萄糖是细胞内的基本组成成分,而GLUT4介导的是诱导吸收的葡萄糖。三种亚型中GLUT3转运效能最高。目前关于GLUTs与心肌缺血再灌注后葡萄糖的摄取、氧化及房颤发生的研究尚处于空白状态,有必要深入研究相关机制。目的：探讨冠心病患者心肌内PGC-1α及GLUT3的蛋白表达水平和相应nRNA表达水平与线粒体功能障碍及CABG术后房颤易感性的关系。方法：入选拟行CABG术的冠心病患者,收集患者术前、术中和术后的资料。术前观察患者心房大小、排空、CRP、血脂血糖水平、肝肾功能等生化指标,在术中开始体外循环前获取右心耳组织超低温保存备分析,术后新发房颤由持续心电监测及心电图评定,观察入选患者术后新发房颤的发生,将新发房颤患者及正常心律患者分组对照,对各组患者基线资料及组织标本中的PGC-1α及GLUT3的蛋白表达水平和相应mRNA表达水平进行对照比较。心肌组织匀浆后PGC-1α及GLUT3的蛋白表达水平用酶联免疫吸附剂测定(enzyme linked immunosorbent assay, ELISA)方法测定；PGC-1α及GLUT3相应mRNA的表达水平采用QRT-PCR方法测定。使用SPSS 13.0等软件进行数据清洗及数据分析,使用Excel、Access、Epiinfo等作为辅助。对数据进行均数、中位数、标准差、频数等描述性分析；t检验、秩和检验、单因素方差分析等单因素分析；多因素相关、logistic回归等多因素分析。结果：共入选79例患者(男性：63人),平均年龄：59.88±8.62年,其中22例患者出现新发房颤。PGC-1α及GLUT3的蛋白及相应mRNA表达水平在发生术后房颤的患者组中明显较低,与POAF明显相关(P0.05)。糖尿病患者中PGC-1 α的蛋白及相应nRN A表达水平也较非糖尿病患者偏低(P0.05)。在多元线性回归模型中,低PGC-1α水平与年龄、糖尿病史、总胆固醇明显相关(P0.05)。结论：心房肌能量代谢的不良调节以及葡萄糖摄取能力的不足先于术后房颤的发生,心房肌组织能量代谢发生障碍的患者发生术后房颤的风险明显增高而且调节心房肌能量代谢的PGC-1α的蛋白及mRNA表达水平减低与糖尿病明显相关。我们的研究提示,心房肌组织能量代谢障碍是导致CABG术后房颤的可能机制。
[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.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R541.75

【共引文献】