从代谢异常机制综述中医药防治糖尿病心肌病研究进展

糖尿病心肌病变是糖尿病的主要并发症之一,与糖尿病病人心力衰竭密切相关。多种因素在糖尿病心肌病变发生、发展过程中发挥重要作用,其早期阶段主要表现为心肌细胞代谢异常。主要从代谢方面阐述近年来糖尿病心肌病发病机制及中医药治疗的研究进展,以供参考。     

他汀类药物对糖尿病心肌病影响的研究进展

正糖尿病心肌病(diabetic cardiomyopathy,DCM)是与糖尿病代谢异常同时发生的,以左心室扩大和弥漫性室壁运动减低,特别是舒张功能低下为特点的心肌结构大范围改变,且不能用高血压性心脏病、冠心病及其他心脏病变来解释的一种独立的特异性心肌病[1]。1972年Rubler等首次提出了DCM的概念[2]。DCM在心肌代谢紊乱和心脏微血管病变的基础上,引起心肌细胞及其间质纤维化,促进心肌重构、心室扩大,出现心功能异常。舒张期功能异常、心室限制是     

老年糖尿病病人心脏病的治疗问题

许多实验室和临床研究指出老化和糖尿病过程可能引起心脏功能及其结构的改变。这些改变与心肌缺血无关。上述两种情况伴有间质胶原的积聚使左室舒张期顺应性降低,并有心室弛缓率降低。在亚临床状态时,衰老的心肌细胞增大,但在糖尿病时并无此种情况描述。在亚临床状态病人中一部分可进展为收缩期功能异常、心力衰竭和心律失常。但尚无确切证据说明两种状态下弥散性心肌病变是由于心壁内小血管病造成的。治疗上需要特别注意强心剂的应用。     

过氧化物酶体增殖物激活受体α与糖尿病心肌病

糖尿病心肌病是常见的糖尿病慢性并发症 ,目前认为能量代谢紊乱在糖尿病心肌病的发病中起重要作用。过氧化物酶体增殖物激活受体α(PPAR α)是一种配体活化型转录因子 ,其主要的生理作用为调节脂肪酸的氧化代谢。在糖尿病个体的心肌细胞中 ,PPAR α表达水平上调 ,由此引起心肌细胞糖脂代谢紊乱 ,最终导致心肌细胞受损、心脏收缩、舒张功能异常及糖尿病心肌病的发生。     

糖尿病心肌病的药物治疗研究进展

糖尿病心肌病（DCM）是糖尿病性心脏病的特异性病变,是糖尿病（DM）心血管并发症的重要组成部分,也是DM患者死亡的主要原因.现已公认,DCM是一个独立的原发病,其发病不依赖于高血压、冠心病和其他已知心脏疾病.DCM早期的主要表现为心肌肥大和舒张功能不全,随后出现心室壁变厚、心肌细胞凋亡和心肌纤维化,晚期主要为收缩功能不全,容易并发心律失常、心力衰竭,甚至猝死.     

线粒体稳态在糖尿病心肌病发生发展中作用的研究进展

糖尿病心肌病是一种发生于糖尿病患者中与冠状动脉疾病等其他心肌病无关的心脏功能障碍, 是导致糖尿病患者心力衰竭及最终死亡的重要原因。糖尿病心肌病的发病机制主要包括氧化应激、炎症反应、细胞凋亡和线粒体稳态失调等。线粒体稳态主要包括线粒体动力学、线粒体氧化代谢和线粒体自噬, 其受多种信号通路的调控, 在维持心肌细胞正常功能中发挥重要作用, 若线粒体稳态失调则会引发氧化应激乃至心肌细胞线粒体网络破碎, 导致脂肪酸累积, 加速糖尿病心肌病的发展。目前, 糖尿病心肌病的发病机制尚未明确, 缺少有效的预防和治疗方法, 该文从线粒体稳态方向阐述糖尿病心肌病发病机制, 为临床治疗提供新的思路和策略。     

过氧化物酶体增殖物激活受体α与糖尿病心肌病

糖尿病心肌病是常见的糖尿病慢性并发症，目前认为能量代谢紊乱在糖尿病心肌病的发病中起重要作用。过氧化物酶体增殖物激活受体α(PPAR-α)是一种配体活化型转录因子，其主要的生理作用为调节脂肪酸的氧化代谢。在糖尿病个体的心肌细胞中，PPAR-α表达水平上调，由此引起心肌细胞糖脂代谢紊乱，最终导致心肌细胞受损、心脏收缩、舒张功能异常及糖尿病心肌病的发生。     

Tako-Tsubo心肌病心室中部气球样变发生率的荟萃分析

目的评估Tako-Tsubo心肌病心室中部气球样变的发生率。方法从PubMed数据库检索以Tako-Tsubo心肌病患者为研究对象、并具体描述心室中部气球样变发生率的文献,对文献描述的心室中部气球样变发生率进行Meta分析。结果共5篇文献入选,分别计算上述文献中心室中部气球样变的发生率、标准误及95%可信区间,经Meta分析得出Tako-Tsubo心肌病心室中部气球样变的发生率为27.4%。结论明确Tako-Tsub6心肌病心室中部气球样变的发生率可能对诊断、治疗Tako-Tsubo心肌病产生影响,可以应用stata软件研究此问题。     

心血管疾病中心肌纤维化与自噬的相关性研究进展

心肌纤维化是由多种病理因素导致心脏疾病发展至一定阶段所具有的共同病理改变,是心室重构的主要原因。心肌纤维化与高血压性心脏病、缺血性心肌病、肥厚性心肌病、扩张性心肌病、病毒性心肌炎及糖尿病心肌病等多种心血管疾病密切相关。自噬在心肌细胞的存活及其维持心肌的收缩功能等方面起着重要作用,有研究显示自噬与心肌纤维化存在一定的联系。本文就心肌纤维化的发病机制及自噬在各种心血管疾病中的作用做一综述,旨在为心肌纤维化的防治提供更为特异和有效的作用靶点。     

扩张型心肌病致病基因的研究进展

扩张型心肌病的主要特点是左心室或双心室扩大、心室收缩功能障碍。它起病隐匿,缺乏特异性治疗,预后较差,大多数患者最终死于充血性心力衰竭。然而,目前扩张型心肌病的发病机制仍不明确,很多与心肌细胞的结构蛋白相关的基因突变可导致扩张型心肌病。该文主要介绍扩张型心肌可能的致病基因及其机制。     

糖尿病心肌病的发病机制和诊断

糖尿病心肌病是排除了高血压、冠心病及其他已知疾病所致的心肌损伤而独立存在的病理生理状态,表现为心脏收缩和(或)舒张功能障碍。其发病机制还不清楚,目前发现与心肌细胞代谢障碍和结构异常、支配心肌的微小血管和自主神经功能紊乱等有关。目前还没有一种特异的诊断方法,一些新的技术包括多普勒组织成像技术、定量组织速度显像和心肌背向散射积分等逐渐应用于临床。本文旨在阐述糖尿病心肌病发病机制和诊断方法的新进展。     

Role of differential signaling pathways and oxidative stress in diabetic cardiomyopathy

Diabetes mellitus increases the risk of heart failure independently of underlying coronary artery disease, and many believe that diabetes leads to cardiomyopathy. The underlying pathogenesis is partially understood. Several factors may contribute to the development of cardiac dysfunction in the absence of coronary artery disease in diabetes mellitus. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Hyperglycemia-induced oxidative stress is a major risk factor for the development of micro-vascular pathogenesis in the diabetic myocardium, which results in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium homeostasis and endothelial dysfunction. Diabetes-mediated biochemical changes show cross-interaction and complex interplay culminating in the activation of several intracellular signaling molecules. Diabetic cardiomyopathy is characterized by morphologic and structural changes in the myocardium and coronary vasculature mediated by the activation of various signaling pathways. This review focuses on the oxidative stress and signaling pathways in the pathogenesis of the cardiovascular complications of diabetes, which underlie the development and progression of diabetic cardiomyopathy.     

糖尿病性心肌病的发病机制及治疗方法研究进展

心血管疾病是2型糖尿病的主要并发症,约占2型糖尿病患者死亡人数的2/3。血糖异常、血脂异常、胰岛素抵抗、慢性低度炎症、氧化应激、内皮功能障碍、血管钙化和高凝状态等多种病理生理过程可加快2型糖尿病患者糖尿病心脏病的进展。糖尿病性心肌病是糖尿病心脏病中较为常见的一种,可导致心功能异常并最终进展为心力衰竭、心律失常,甚至猝死。本文综述了糖尿病性心肌病的发病机制,以及当前及未来潜在的治疗方法。     

Diabetic cardiomyopathy,causes and effects

Diabetes is associated with increased incidence of heart failure even after controlling for coronary artery disease and hypertension. Thus, as diabetic cardiomyopathy has become an increasingly recognized entity among clinicians, a better understanding of its pathophysiology is necessary for early diagnosis and the development of treatment strategies for diabetes-associated cardiovascular dysfunction. We will review recent basic and clinical research into the manifestations and the pathophysiological mechanisms of diabetic cardiomyopathy. The discussion will be focused on the structural, functional and metabolic changes that occur in the myocardium in diabetes and how these changes may contribute to the development of diabetic cardiomyopathy in affected humans and relevant animal models.     

Diabetic cardiomyopathy and its mechanisms: Role of oxidative stress and damage

Diabetic cardiomyopathy as an important threat to health occurs with or without coexistence of vascular diseases. The exact mechanisms underlying the disease remain incompletely clear. Although several pathological mechanisms responsible for diabetic cardiomyopathy have been proposed, oxidative stress is widely considered as one of the major causes for the pathogenesis of the disease. Hyperglycemia‐, hyperlipidemia‐, hypertension‐ and inflammation‐induced oxidative stress are major risk factors for the development of microvascular pathogenesis in the diabetic myocardium, which results in abnormal gene expression, altered signal transduction and the activation of pathways leading to programmed myocardial cell deaths. In the present article, we aim to provide an extensive review of the role of oxidative stress and anti‐oxidants in diabetic cardiomyopathy based on our own works and literature information available.     

运动改善糖尿病心肌病的机制

糖尿病心肌病是糖尿病严重的并发症之一,也是糖尿病患者发生猝死的主要原因之一.目前研究显示,运动是改善糖尿病心肌损害的重要的非药物干预措施.它可以通过改善心肌代谢、增强Ca2调控、保护细胞内线粒体功能等,实现抑制心肌细胞凋亡、心肌微血管病变、心肌纤维化等作用,最终缓解糖尿病并发症的发生、发展.阐述运动对糖尿病心肌的作用机制,可为延缓甚至逆转糖尿病心肌病进展及心肌重构,防止其转变为心功能不全甚至心力衰竭提供新的理论依据.     

Oxidative stress and diabetic cardiomyopathy: a brief review

Diabetes is a serious public health problem. Improvements in the treatment of noncardiac complications from diabetes have resulted in heart disease becoming a leading cause of death in diabetic patients. Several cardiovascular pathological consequences of diabetes such as hypertension affect the heart to varying degrees. However, hyperglycemia, as an independent risk factor, directly causes cardiac damage and leads to diabetic cardiomyopathy. Diabetic cardiomyopathy can occur independent of vascular disease, although the mechanisms are largely unknown. Previous studies have paid little attention to the direct effects of hyperglycemia on cardiac myocytes, and most studies, especially in vitro, have mainly focused on the molecular mechanisms underlying pathogenic alterations in vascular smooth-muscle cells and endothelial cells. Thus, a comprehensive understanding of the mechanisms of diabetic cardiomyopathy is urgently needed to develop approaches for the prevention and treatment of diabetic cardiac complications. This review provides a survey of current understanding of diabetic cardiomyopathy. Current consensus is that hyperglycemia results in the production of reactive oxygen and nitrogen species, which leads to oxidative myocardial injury. Alterations in myocardial structure and function occur in the late stage of diabetes. These chronic alterations are believed to result from acute cardiac responses to suddenly increased glucose levels at the early stage of diabetes. Oxidative stress, induced by reactive oxygen and nitrogen species derived from hyperglycemia, causes abnormal gene expression, altered signal transduction, and the activation of pathways leading to programmed myocardial cell deaths. The resulting myocardial cell loss thus plays a critical role in the development of diabetic cardiomyopathy. Advances in the application of various strategies for targeting the prevention of hyperglycemia-induced oxidative myocardial injury may be fruitful.     

Expression changes of thrombospondin-1 and neuropeptide Y in myocardium of STZ-induced rats

Diabetic cardiomyopathy was the most dangerous diabetic complication facing diabetics, with its exact mechanisms remaining obscure. Our study was conducted to investigate the expression of thrombospondin-1 (TSP-1) and neuropeptide Y (NPY) in myocardium of streptozotocin (STZ)-induced diabetic rats. We employed streptozotocin (STZ)-induced diabetic rats to study the alteration of the TSP-1 and NPY expression in the left ventricle myocardium in diabetic and normal group by immunohistochemistry and immunofluorescence. The data of weight, blood sugar and urine sugar indicated no significant difference between the two groups before the animal model was induced. Four weeks after the induction of diabetes the weight of the diabeteic animals was 189.1+/-18.4 g, plasma glucose was 23.7+/-3.25 mmol/L and urine glucose was (++) to (+++); whereas the weight of the control animals was 260.5+/-32.1 g, plasma glucose was 4.9+/-0.5 mmol/L and urine glucose undetectable (-). The differences between the control and the diabetes group were distinct. A significant increase of the TSP-1 and NPY expression was also observed in the diabetic rat's heart. The number of the NPY positive myocardium and the light density of the positive myocardium in the left ventricle of the diabetic model were 17.3+/-2.1 and 102.5+/-9.3/mm(2), respectively, which were considered as increased when compared with the control that were 10.1+/-2.6 and 61.2+/-6.7, respectively. Our results support the view that high glucose conditions can induce an increased synthesis of TSP-1 through the PKC-TGF-beta-TSP-1 pathway, which in turn facilitate TGF-beta activation. Additionally, the activation of PKC may further lead to the over-expression of NPY. This may be involved in diabetic cardiomyopathy.     

Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis

In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies are termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies is imperative. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in cardiac function are typically manifested as abnormal diastolic function that with time leads to loss of contractile function. Echocardiography based methods currently stand as the preferred diagnostic approach for diabetic cardiomyopathy, due to its wide availability and economical use. In addition to conventional techniques, magnetic resonance imaging and spectroscopy along with contrast agents are now leading new approaches in the diagnosis of myocardial fibrosis, and cardiac and hepatic metabolic changes. These strategies can be complemented with serum biomarkers so they can offer a clear picture as to diabetes-induced changes in cardiac structure/function even at very early stages of the disease. This review article intends to provide a summary of experimental and routine tools currently available to diagnose diabetic cardiomyopathy induced changes in cardiac structure/function. These tools can be reliably used in either experimental models of diabetes or for clinical applications.