帕金森病的线粒体功能障碍与氧化应激

帕金森病(PD)是一种中老年人神经系统变性疾病,其病因和发病机制至今仍未明确,大量研究表明线粒体功能障碍、氧化应激、细胞凋亡、兴奋性氨基酸毒性、炎症反应都参与了帕金森病的发病过程.线粒体功能障碍与氧化应激一直是研究的热点,现主要就帕金森病的线粒体功能障碍与氧化应激做一综述.     

线粒体功能障碍与心力衰竭的关系

线粒体是真核细胞内重要的细胞器,在细胞能量代谢、信号转导以及氧化应激、钙稳态和细胞凋亡调节过程中均发挥着重要的作用。因此,线粒体功能正常在生命活动中至关重要。线粒体功能障碍的机制复杂多样并相互联系、相互影响;越来越多的研究表明,线粒体功能障碍是心力衰竭进展中的关键因素之一。因此,认识和深入研究线粒体功能障碍在心力衰竭发生发展中的作用,为阐明心力衰竭的发病机制及其临床防治拓开了新的思路。     

线粒体功能障碍与年龄相关性黄斑变性研究进展

<正>线粒体在不同的细胞中密度不同,在代谢活跃的细胞如视网膜色素上皮细胞中大量表达。氧化性损伤导致的线粒体功能障碍已经成为衰老性疾病的发病机制之一〔1〕。越来越多的证据表明线粒体功能障碍与视网膜疾病之间存在联系。1线粒体是细胞功能和代谢方面起重要作用的细胞器它的主要作用是产生腺苷三磷酸,控制细胞代谢和调节细胞凋亡,线粒体内膜和外膜由磷脂双分子层组成,含有大量的镶嵌蛋白。线粒体基因组不稳定性是年龄相关性疾病的促成因素。由氧化性应激导致的线粒体功能障碍在年龄相关性黄     

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。     

线粒体功能障碍在心血管疾病中的作用

心血管疾病(CVD)在世界范围内分布广泛,是导致人类死亡的主要原因之一。CVD有着复杂的病因,多种危险因素和病理机制可导致CVD。在细胞中,代谢异常、活性氧的过量产生、能量供应不足、自噬功能障碍、内质网应激和凋亡的激活等各种异常均可导致线粒体功能障碍。最近研究表明线粒体功能障碍在CVD的发生和发展中起着关键作用。现强调心肌细胞内线粒体功能障碍在CVD中的相关作用机制,为找到疾病新的治疗靶点带来启发。     

线粒体功能障碍及炎症与衰老的相关关系

线粒体功能障碍和炎症是衰老及慢性退行性疾病的标志。线粒体功能障碍可能是引发衰老的始动因素,在衰老过程中,线粒体DNA发生不同程度的氧化损伤,导致细胞的能量代谢受损,细胞功能障碍,甚至死亡。同时衰老机体持续存在的低级别炎症反应可通过多种作用损害免疫系统的活化,而炎症代谢产物在调节免疫应答中的作用可为干预年龄相关疾病的病理过程提供依据。     

氧化应激相关线粒体功能障碍与支气管哮喘

支气管哮喘(简称哮喘)是一种以不同程度的气流阻塞、气道高反应性和气道炎症为特点的复杂的炎症性疾病,受到遗传和环境因素的共同影响.分子生物学、细胞学以及动物模型研究提示线粒体功能障碍和氧化应激在哮喘发病中起着重要作用.哮喘状态下,炎症细胞内活性氧自由基生成增加,线粒体功能出现障碍,同时伴随气道上皮细胞损伤,并影响气道平滑肌功能.过敏性哮喘小鼠模型研究以及利用哮喘患者的外周细胞和组织进行的研究提示,抗氧化治疗有望成为哮喘预防与治疗的有效方法.本文将主要对以下方面进行讨论:①健康状态下的线粒体结构与功能;②氧化应激与线粒体功能障碍;③肺部氧化应激的来源及中和机制;④哮喘状态下的氧化应激和线粒体功能障碍;⑤线粒体靶向抗氧化剂的研究进展.     

血管内皮功能障碍与高血压

血管内皮功能障碍与高血压密切相关。一方面血管内皮功能障碍在高血压的发生、发展过程中起重要作用;另一方面高血压本身又加重血管内皮功能障碍,形成恶性循环。现综述血管内皮细胞的生理功能、血管内皮功能障碍的相关因素、血管内皮功能障碍与高血压关系、血管内皮功能检测及血管内皮功能障碍的修复等方面的研究进展。     

线粒体功能障碍与肥胖性脂肪肝

线粒体在脂肪酸的β氧化、ATP合成和活性氧形成中起重要作用，在许多疾病中可发现线粒体的功能障碍。线粒体功能障碍有其导致的线粒体能量储备减少和氧化应激增强，导致脂肪为性的肝细胞对二次打击的反应能力降低，进而在肥胖性脂肪肝的发生和发展中起重要作用。     

阿尔茨海默病患者线粒体功能障碍的发生机制研究进展

阿尔茨海默病（AD）是日常生活中常见的神经退行性疾病之一,其致病机制仍不明确。线粒体作为生物能量、钙信号传导和氧化还原稳态等方面发挥至关重要作用的细胞器,其功能出现障碍可导致细胞能量缺乏、细胞内钙失衡和氧化应激,从而进一步加重Aβ和Tau蛋白的影响,导致突触功能障碍、认知障碍甚至记忆丧失。随着对AD发病机制的不断深入研究,氧化应激、线粒体动力学及线粒体自噬被认为与AD的发病过程密切相关。氧化应激引起的线粒体功能障碍会进一步导致Aβ蛋白的聚集和Tau蛋白的过度磷酸化,而Aβ蛋白的聚集和高度磷酸化的Tau蛋白可损害线粒体功能,从而形成恶性循环。GTP相关的动力相关蛋白1(Drp1)表达水平异常可导致线粒体过度分裂甚至碎片化,引起线粒体功能障碍和神经元损伤,最终导致疾病的发生。线粒体自噬功能异常在AD发病中发挥着重要的作用,有多种通路介导的线粒体自噬途径参与了AD的发病,包括Aβ蛋白积聚诱导的线粒体自噬途径、氧化应激诱导的线粒体自噬途径、PINK1-Parkin通路介导的线粒体自噬途径以及受体介导的线粒体自噬途径等,均可引起异常线粒体的堆积导致线粒体功能障碍,进而诱导AD发病。     

Mitochondrial DNA alterations and mitochondrial dysfunction in the progression of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most common malignancies and is ranked third in mortality among cancer-related diseases.Mitochondria are intracellular organelles that are responsible for energy metabolism and cellular homeostasis,and mitochondrial dysfunction has been regarded as a hallmark of cancer.Over the past decades,several types of mitochondrial DNA(mtDNA)alterations have been identified in human cancers,including HCC.However,the role of these mtDNA alterations in cancer progression is unclear.In this review,we summarize the recent findings on the somatic mtDNA alterations identified in HCC and their relationships with the clinicopathological features of HCC.Recent advances in understanding the potential roles of somatic mtDNA alterations in the progression of HCC are also discussed.We suggest that somatic mtDNA mutations and a decrease in the mtDNA copy number are common events in HCC and that a mitochondrial dysfunction-activated signaling cascade may play an important role in the progression of HCC.Elucidation of the retrograde signaling pathways in HCC and the quest for strategies to block some of these pathways will be instrumental for the development of novel treatments for this and other malignancies.     

细胞因子与高血压病心功能不全的相关性研究

目的　观察高血压病 (EH)心衰患者细胞因子白细胞介素 6(IL- 6)、白细胞介素 8(IL- 8)、肿瘤坏死因子 α(TNF- α)、γ干扰素 (IFN- γ)及 Apo- 1 / Fas的变化 ,分析心功能改变与细胞因子相关性 ,以期为临床应用更有效的干预治疗提供理论依据。方法　采用 ELISA法检测 60例高血压病患者和 2 0例正常对照组血清各炎性细胞因子浓度 ,并应用彩色多普勒超声心动图测定其左室收缩及舒张功能 ,分析心功能改变与细胞因子相关性。结果　与正常对照组比较 EH组的血清细胞因子含量明显升高 ,增高的程度与心衰的严重程度相一致 ,心功能不全组间比较也有明显差别 ,EH组收缩功能减退及舒张功能减退与炎性细胞因子的增高密切相关。结论　高血压病心衰患者存在着细胞因子的过度激活及心肌细胞的凋亡 ,并与心衰程度加重密切相关 ,在心衰的发生发展中起着重要的作用     

老年高血压病并肾功能损害的综合康复治疗

目的 :研究综合康复治疗对老年高血压病并肾功能损害的临床疗效。方法 :对 2 75例老年高血压病并肾功能损害者 ,给予综合康复治疗 3～ 6个月 ,随访 2～ 3年。结果 :治疗组总有效率 90 .18% ,而10 0例对照组总有效率为 80 .0 0 %。结论 :综合康复治疗对老年高血压病并肾功能损害的临床疗效优于单纯药物治疗。     

Microvascular dysfunction as a link between obesity,insulin resistance and hypertension

Impaired microvascular dilatation from any cause and impaired insulin-mediated capillary recruitment in particular result in suboptimal delivery of glucose and insulin to skeletal muscle, and subsequently impairment of glucose disposal (insulin resistance). In addition, microvascular dysfunction, through functional and/or structural arteriolar and capillary drop-out, and arteriolar constriction, increases peripheral resistance and thus blood pressure. Microvascular dysfunction may thus constitute a pathway that links insulin resistance and hypertension. Overweight and obesity may be an important cause of microvascular dysfunction. Mechanisms linking overweight and obesity to microvascular dysfunction include changes in the secretion of adipokines leading to increased levels of free fatty acids and inflammatory mediators, and decreased levels of adiponectin all of which may impair endothelial insulin signaling. Microvascular dysfunction may thus constitute a new treatment target in the prevention of type 2 diabetes mellitus and hypertension.     

Mitochondrial metabolism and diabetes

The oversupply of calories and sedentary lifestyle has resulted in a rapid increase of diabetes prevalence worldwide. During the past two decades, lines of evidence suggest that mitochondrial dysfunction plays a key role in the pathophysiology of diabetes. Mitochondria are vital to most of the eukaryotic cells as they provide energy in the form of adenosine triphosphate by oxidative phosphorylation. In addition, mitochondrial function is an integral part of glucose‐stimulated insulin secretion in pancreatic β‐cells. In the present article, we will briefly review the major functions of mitochondria in regard to energy metabolism, and discuss the genetic and environmental factors causing mitochondrial dysfunction in diabetes. In addition, the pathophysiological role of mitochondrial dysfunction in insulin resistance and β‐cell dysfunction are discussed. We argue that mitochondrial dysfunction could be the central defect causing the abnormal glucose metabolism in the diabetic state. A deeper understanding of the role of mitochondria in diabetes will provide us with novel insights in the pathophysiology of diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00047.x, 2010)     

高血压患者血浆BNP水平与左心功能不全的关系

目的探讨正常人群、原发性高血压及伴左室功能不全的患者脑钠素(BNP)的血浆浓度及其关系,为BNP诊断高血压心脏病(左室肥厚)提供理论依据。方法应用免疫放射法测定血浆BNP水平。选择住院原发性高血压Ⅰ～Ⅲ期患者72例,按照美国纽约心脏病协会(NYHA)心功能分级分为2组,NYHAⅠ～Ⅱ级35例,NYHAⅢ～Ⅳ级37例,以左室射血分数(LVEF)≤45%作为心功能不全诊断的标准。并以30例健康人作对照比较。结果原发性高血压组和原发性高血压伴左室肥厚组的血浆BNP平均水平均显著高于对照组(P<0.01)。结论血浆BNP是判断原发性高血压患者预后和进行危险分层的敏感指标,不仅与脉压、左室质量指数、左室舒张功能等密切相关,而且对判断左心功能不全的程度及预后都有一定的意义。     

Management of erectile dysfunction in hypertension:Tips and tricks

Arterial hypertension is a major risk factor for cardiovascular disease and affects approximately one third of the adult population worldwide. The vascular origin of erectile dysfunction is now widely accepted in the vast majority of cases. Erectile dysfunction is frequently encountered in patients with arterial hypertension and greatly affects their quality of life of hypertensive patients and their sexual partners. Therefore, the management of erectile dysfunction in hypertensive patients is of paramount importance. Unfortunately, erectile dysfunction remains under-reported, under-recognized, and under-treated in hypertensive patients, mainly due to the lack of familiarity with this clinical entity by treating physicians. This review aims to discuss the more frequent problems in the management of hypertensive patients with erectile dysfunction and propose ways to overcome these problems in everyday clinical practice.