线粒体动力学和线粒体自噬与心血管疾病的研究进展

线粒体是一种动态的细胞器,通过响应各种代谢和环境的信号,分裂和融合改变其形态和结构,从而维持细胞的正常功能.它们短暂而快速的形态变化对于细胞周期、免疫、凋亡和线粒体质量控制等许多复杂的细胞过程至关重要.线粒体自噬与线粒体质量控制密切相关,通过将受损的功能障碍的线粒体转运到溶酶体进行降解,促进心肌细胞受损线粒体的更新,并...     

线粒体质量控制与心血管疾病

心肌线粒体是心脏能量代谢的主要部位,其功能障碍可导致多种心血管疾病.线粒体质量控制主要通过调控线粒体的生物发生、融合、分裂和自噬,以保证线粒体形态、数量和质量的相对稳定,以维持其结构和功能的完整性.线粒体的质量控制体系在缺血性心脏病、糖尿病性心肌病、心力衰竭、动脉粥样硬化和高血压中发挥重要作用.     

线粒体质量控制在2型糖尿病发生发展及治疗中的作用研究进展

线粒体作为细胞能量代谢的核心参与者，参与了胰岛素抵抗和2型糖尿病发生机制。线粒体质量控制系统包括线粒体生物合成、线粒体动力学、线粒体自噬。线粒体质量控制通过不断融合/分裂改变其形状及大小、生物合成新生线粒体补充线粒体池和自噬将包裹受损的线粒体传递至溶酶体进行清除，维持相对稳定的线粒体数量和质量的动态过程，是保证线粒体健康和维持线粒体稳态的重要机制。糖尿病患者在线粒体自噬、动力学和生物合成方面存在缺陷，即线粒体质量控制失调，导致线粒体功能障碍，诱发β细胞功能紊乱甚至死亡。深入了解线粒体质量控制与T2DM的关系，通过调节线粒体生物合成、线粒体融合/分裂和线粒体自噬等相关因子表达，影响线粒体质量控制，从而改善外周组织的胰岛素敏感性、提高葡萄糖刺激胰岛素分泌能力、促进白色脂肪褐变和减少脂肪异位沉积，达到降糖、降脂、治疗T2DM的目的。     

线粒体融合蛋白2在心血管疾病中的研究现状

线粒体是一个处于不断地融合与分裂过程中的动态细胞器。线粒体融合蛋白2(Mfn2)作为广泛分布于线粒体外膜和线粒体结合内质网膜上具有多重功能的蛋白,参与维持正常细胞功能。除了参与线粒体融合外,Mfn2还能够调节线粒体代谢、促进损伤线粒体的自噬、增强线粒体与内质网交流、维持内质网功能及通过调控线粒体外膜通透性和渗透性钙转运孔道的启闭参与细胞死亡过程等。另外,Mfn2基因还可通过调控Ras-Raf-ERK/MAPK和Ras-PI3K-Akt信号通路分别参与调控血管平滑肌细胞的增殖和凋亡过程。Mfn2的这一系列重要的生物学功能有助于其参与高血压、肺动脉高压、动脉粥样硬化、急性缺血/再灌损伤、扩张性心肌病、心肌肥大、心衰和肥胖糖尿病等多种心血管疾病的发生发展过程。研究Mfn2与心血管疾病的相关性也许能为临床提供一个心血管疾病潜在治疗的靶点。因此,本文将综述Mfn2在心血管疾病相关研究中的现状。     

线粒体自噬与心脏能量代谢研究进展

<正>线粒体是真核细胞能量产生的主要场所,其通过氧化磷酸化的形式为机体提供ATP,维持细胞的基础代谢。外界刺激或病理环境可导致线粒体结构和功能受损,最终导致ATP合成受限。线粒体自噬通过选择性清除该类功能障碍线粒体,保持细胞内线粒体数量的平衡性、结构和功能的完整性,维持细胞内环境稳态,并促进细胞的存活,对保证机体的能量供应至关重要。近年研究表明,线粒体自噬异常会导     

微小RNA对缺血再灌注损伤心肌线粒体作用的研究进展

心肌缺血再灌注损伤是造成心肌结构损伤、功能障碍的一种病理生理过程,进一步发展会导致级联的多器官功能障碍。线粒体是一种结构功能复杂且对外界环境反应敏感的细胞器,其稳态的维持依赖于正常形态、功能及数量的相对稳定状态。线粒体质量与代谢异常和心血管疾病尤其是心肌缺血再灌注损伤的发生密切相关。微小RNA是近年来研究较多的在缺血再灌注损伤心肌线粒体保护中具有重要作用的调控因子。本文通过微小RNA对心肌缺血再灌注损伤时线粒体形态、功能、线粒体自噬和线粒体DNA几个方面的调控机制与相关前沿进展进行综述,为微小RNA参与缺血再灌注心肌线粒体损伤的后续研究提供一定的理论依据。     

线粒体功能障碍与血管内皮损伤的研究进展

线粒体功能障碍会导致ATP的生成减少,活性氧的产生增加,被认为是血管内皮损伤的触发因素之一。许多因素与线粒体功能障碍有关,如线粒体DNA突变、线粒体融合与分裂失衡、线粒体自噬受损等。本文综述了线粒体的质量控制过程和线粒体功能障碍在血管内皮损伤中的作用机制,以期为动脉粥样硬化的有效防治提供新的思路。     

线粒体质量控制与围生期心脏发育的相关研究进展

心脏作为哺乳动物能量消耗最高的器官之一,其在围生期发育过程中需要完成从无氧糖酵解到脂肪酸氧化的能量代谢转换,期间心肌细胞线粒体发育迅速,以满足心脏对能量的需要。近年来研究发现线粒体质量控制在围生期心脏发育成熟过程中发挥重要作用。线粒体质量控制包括线粒体生物合成、线粒体融合/分裂以及线粒体自噬等过程,通过维持线粒体结构及功能的完整来保证细胞功能及代谢的正常。本文就哺乳类动物心脏发育过程中线粒体质量控制系统的变化及其在心脏发育中的作用进行综述。     

线粒体自噬在心血管疾病中的作用

自噬对于组成心血管系统的细胞（如心肌细胞、内皮细胞和血管平滑肌细胞等）的细胞内稳态和生理功能的维持具有重要作用。线粒体自噬是以损伤的线粒体作为自噬底物的一种选择性自噬。由于线粒体是生物能量的主要来源且心血管系统对能量要求较高，线粒体自噬在心血管稳态的维持中尤为重要。研究证实线粒体自噬在心肌梗死、心力衰竭和动脉粥样硬化等疾病中扮演重要角色。本文概述了线粒体自噬的主要调控通路，并阐述了线粒体自噬与心血管疾病之间的密切联系。     

线粒体动力学异常与相关心血管疾病

线粒体是心肌能量代谢的主要场所,其通过分裂和融合的动态平衡维持正常的形态和功能.线粒体分裂和融合的动态转换称为线粒体动力学,受线粒体融合和分裂相关蛋白等多种蛋白调控.线粒体动力失衡可引起心脏结构和功能的紊乱,参与扩张型心肌病、缺血再灌注损伤、脓毒性心肌病、糖尿病心肌病和动脉粥样硬化等心血管疾病的发生和发展.维持线粒体动...     

Alzheimer disease as a vascular disorder: Where do mitochondria fit?

Although the precise culprit in the etiopathogenesis of Alzheimer disease (AD) is still obscure, defective mitochondria functioning has been proposed to be an upstream event in AD. Mitochondria fulfill a number of essential cellular functions, and it is recognized that the strict regulation of the structure, function and turnover of these organelles is an immutable control node for the maintenance of neuronal and vascular homeostasis. Extensive research in postmortem brain tissue from AD subjects, and AD animal and cellular models revealed that mitochondria undergo multiple malfunctions during the course of this disease. The present review summarizes the current views on how mitochondria are implicated in both AD-related neuronal and cerebrovascular degeneration. The understanding of the mitochondrial mechanisms underlying AD pathology is critical to design more effective strategies to halt or delay disease progression.     

Normothermic ischaemic cardiac arrest and reperfusion of the isolated working heart: effect of chlorpromazine on functional, metabolic and morphological recovery

The effects of chlorpromazine, an inhibitor of both Ca2+ flux and phospholipase activity, on myocardial ultrastructure, function and metabolism were assessed during normothermic ischaemic cardiac arrest and reperfusion of the isolated working rat heart. Normothermic ischaemic cardiac arrest produced significant changes in myocardial ultrastructure, high energy phosphate contents and mitochondrial oxidative phosphorylation within 20 min. Reperfusion of untreated hearts subjected to 20 and 25 min ischaemia failed to restore mitochondrial function, mechanical activity and ATP content to control, pre-ischaemic levels. Morphological signs of ischaemic injury regressed, especially in the subendocardial layer. Pretreatment of hearts with chlorpromazine did not prevent the ischaemia-induced changes in myocardial ultrastructure and mitochondrial function. However, during reperfusion the chlorpromazine-treated, totally ischaemic heats (20 to 25 min) exhibited improved coronary flow rates, and ultrastructural and mechanical recovery. The mitochondrial oxidative phosphorylation process and tissue high energy phosphate contents were not affected by the drug.     

抗线粒体抗体在MELAS综合征脑活检组织的表达观察

目的 对线粒体脑肌病伴随乳酸血症和卒中样发作(MELAS综合征)患者脑活检以探讨其病理变化及发病机制.方法 收集海军总医院确诊的3例MELAS综合征患者脑活检组织石蜡标本,行AMA免疫组化染色.结果 3例MELAS综合征患者脑组织AMA免疫组化染色光镜观察发现病变脑组织及蛛网膜下腔小血管异常增生,血管肇薄厚不均,可见到大量浓染的棕褐色沉积物;神经元细胞中也可见到大量浓染的棕褐色沉积物.结论 MELAS综合征患者AMA免疫组化染色的主要病理特点是病变部位血管异常增生,提示病变部位血管平滑肌、内皮细胞及神经细胞内大量异常线粒体堆积,与电镜下发现大量异常线粒体堆积对线粒体脑肌病的诊断有同样价值.     

Histopathological observation of the heart with diffuse and abnormal proliferation of mitochondria in myocardial cells (mitochondrial cardiomyopathy): Report of an adult case

Summary An autopsy case of idiopathic dilated cardiomyopathy with abnormal proliferation of mitochondria in the myocardial cells is reported. The case is that of a 39-year-old male with congestive heart failure. The heart was 700 g and showed marked dilatation of all cardiac chambers with myocardial fibrosis of the left ventricular myocardium and interventricular septum, especially in the basal portion of the left ventricular posterior wall. Myocardial cells were hypertrophied with a marked increase of fine-granular sarcoplasm, containing numerous mitochondria, seen by electron microscopy. The mitochondria were usually round or oval and ranged in size from 0.3 to 1.2 µm in diameter. The cristae of these mitochondria frequently showed a concentric lamellar or reticular configuration. Myofibrils were unusually scarce, but the sarcomere structure and arrangement of myofilaments were well-preserved. Epicardial and intramural coronary vessels were almost normal. From these findings, we consider this to be an adult case of mitochondrial cardiomyopathy.     

线粒体突变及不稳定在胃癌中的研究

目的 探讨线粒体突变及不稳定在胃癌发生、发展中的作用.方法 利用激光显微切割技术分离胃癌组织及其切缘的正常组织,应用变性高效液相色谱DHPLC对胃癌线粒体D-loop调控区D-loop-(CA)n进行突变筛查及测序分析,同时进行线粒体D-loop非编码区(CA)n重复序列的不稳定(mtMSI)检测.结果 胃癌组织样本中D-loop-(CA)n调控区基因突变率为50.8％ (31/61),正常组织均未见有序列改变.29.5％ (18/61)发生线粒体重复序列(CA)n的不稳定.18例线粒体不稳定(mtMSI)中有16.4％(10/61)同时发生D-loop点突变,有8例同时存在核不稳定(nMSI-H).结论 胃癌mtDNA异常参与了肿瘤的发生、发展.     

Observation of a second phosphate pool in the perfused heart by 31P NMR; is this the mitochondrial phosphate?

We report here our observations on perfused rat hearts using ³¹P NMR which show that inorganic phosphate (P_i) is located in two regions of differing pH. From the chemical shifts of the P_i signals and their behaviour under various stimuli we identify one signal (pH 7.0) as coming from the cytosol and suggest that the other (pH 7.38) comes from the mitochondrial matrix space.     

Observation of a second phosphate pool in the perfused heart by P NMR; is this the mitochondrial phosphate?

We report here our observations on perfused rat hearts using ³¹P NMR which show that inorganic phosphate (P_i) is located in two regions of differing pH. From the chemical shifts of the P_i signals and their behaviour under various stimuli we identify one signal (pH 7.0) as coming from the cytosol and suggest that the other (pH 7.38) comes from the mitochondrial matrix space.