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1.
肾素-血管紧张素系统过度激活导致血管氧化应激损伤,进而影响血管功能.xanthine氧化酶、NAD(P)H氧化酶和脱耦联的NO合酶是血管组织中活性氧的主要来源.超氧化物阴离子和活性氧簇中的其他成分通过多种机制失活NO在心血管疾病的发生和发展中具有重要作用.随着对氧化应激损伤参与血管反应性调节机制的认识逐渐加深,有希望通过抑制氧化应激损伤改善血管内皮功能.  相似文献   

2.
解偶联蛋白2(UCP2)是核DNA编码的线粒体内膜阴离子转运体,广泛存在多种组织和器官中。其通过耗散线粒体内膜质子梯度发挥可诱导的解偶联作用。内皮细胞损伤是多种血管疾病的始动环节,近年来的研究发现,UCP2在动脉粥样硬化、高血压、糖尿病等中发挥血管内皮保护作用。本文对UCP2内皮保护作用的相关机制作一综述。  相似文献   

3.
田萌  吴媛媛  谢锋  卫培峰  陈琳  李敏 《生命科学》2020,32(5):453-460
瞬时受体电位(TRP)通道是一类重要的非选择性阳离子通道,其家族成员众多,参与多种生理病理过程。其中,TRP通道的异常表达及功能改变与心脑血管疾病的发生发展密切相关。近年研究发现,通过拮抗或者激活TRP通道可以调节血管内皮和血管平滑肌功能,参与心脑血管疾病的调控。该文主要从TRP通道的结构及各亚家族蛋白基于血管内皮和血管平滑肌对心脑血管系统疾病的作用及机制作一综述,为心脑血管疾病的防治提供新思路。  相似文献   

4.
氧化应激是一种氧化还原失衡的状态,易引起生物体组织细胞发生氧化损伤。通过激活抗氧化系统调节氧化还原平衡是生物体内普遍存在的氧化应激响应机制。硫化氢(hydrogen sulfide, H2S)是生物体内重要的信号分子,它能通过多种途径调节机体生理反应和胁迫响应。本文综述了植物中H2S的产生途径,H2S常见供体的特性,H2S、活性氧(reactive oxygen species, ROS)和活性氮(reactive nitrogen species, RNS)在调节植物氧化应激响应中的研究进展;重点讨论了H2S调节植物氧化应激响应的方式,及其与ROS和RNS在植物氧化还原平衡调节中的相互作用调控,为理解植物氧化应激响应过程中信号分子的作用机制提供参考。  相似文献   

5.
解偶联蛋白(uncoupling protein,UCP)属于线粒体内膜上的一类载体蛋白,其生理作用是消除线粒体膜电位,使氧化磷酸化解偶联,从而抑制酸腺苷(adenosine triphosphate,ATP)合成,能量以热能形式散发.研究发现UCP2具有一种质子漏功能,表现对线粒体活性氧(reactive oxygen species,ROS)产生的调控和降低ROS的功能.在不同组织器官,不同代谢状态下UCP2的生理功能对细胞的影响不完全相同.特别是近年来的研究发现,UCP2参与了能量代谢、ROS的产生、子宫内膜退化、衰老等过程,并且与非酒精性脂肪肝、抗肥胖、动脉粥样硬化、局部缺血以及缺血再灌注损伤和2型糖尿病等有一定的相关性,倍受人们的关注.  相似文献   

6.
解偶联蛋白2对活性氧的抑制作用   总被引:1,自引:0,他引:1  
线粒体在能量代谢和自由基代谢中占据十分重要的地位。电子传递过程中形成的活性氧(reactive oxygen species,ROS)履行着众多生理功能,但过多或持续存在的ROS可能与癌症、衰老、糖尿病、动脉硬化、局部缺血或再灌注损伤等的发生有关。解偶联蛋白2(uncoupling protein 2,UCP2)作为线粒体内膜质子转运家族中的一个新成员,通过解偶联作用能降低线粒体内膜电势,使活性氢产生减少。UCP2抑制ROS产生的作用日益受到关注。  相似文献   

7.
Li WG  Ren CH  Zhang CG 《生理科学进展》2010,41(3):197-200
脑红蛋白(NGB)是神经系统特异性携氧珠蛋白,可作为内源性神经保护因子保护神经元免受缺血/缺氧性损伤。活性氧(ROS)是机体正常代谢的中间产物,生理状态下体内ROS处于产生与清除的动态平衡中。机体内过多的ROS是产生氧化应激的重要因素,也是导致多种疾病包括神经系统疾病的重要原因,因此清除体内过多的ROS是防治神经系统疾病的重要措施。目前已发现NGB在清除过多ROS方面可能起重要作用,这对调节ROS的内稳态水平具有重要意义。本文就NGB对ROS的清除作用及其在神经系统疾病中的功能意义进行综述。  相似文献   

8.
阿尔茨海默病(Alzheimer’s disease, AD)是一种神经退行性疾病,其病因复杂。活性氧(reactive oxygen species, ROS)是生理代谢的副产物,机体中有多个ROS来源,异常水平的ROS会破坏抗氧化系统并产生氧化应激现象。越来越多的证据表明,氧化应激可能是认知老化和诱发AD的关键因素之一。本文综述了机体中氧化应激的来源,并分析了氧化应激对自噬功能、β-淀粉样蛋白(amyloid-β, Aβ)、Tau蛋白、突触功能障碍以及风险基因ApoE ε4的影响,探讨了针对氧化损伤的干预措施,为AD的发病机制研究和潜在治疗策略提供参考。  相似文献   

9.
糖尿病(DM)导致的心脑血管并发症是危害人类健康的重大疾病。氧化应激被认为是DM相关心血管并发症发生、发展的重要机制,但通过补充外源性抗氧化剂并未能使心血管疾病患者远期获益。核因子E2相关因子2(Nrf2)可增加内源性抗氧化酶的活性从而提高机体的抗氧化应激能力,可能是治疗糖尿病心血管并发症的一个重要靶点,提示靶向Nrf2药物的开发可能获得防治糖尿病相关血管并发症的新一代药物。本文就Nrf2在糖尿病相关心血管并发症发生、发展中的作用及其药理性活化剂对糖尿病(DM)相关心血管病变的治疗作用进行综述。  相似文献   

10.
本文从4个方面综述并讨论了血管病变机制与血管功能调控研究的重要意义、现状与发展趋势:(1)血管病变的机制研究是重大的社会需求,而且是国际医学领域关注的重要热点问题;(2)血管病变机制与血管功能调控研究的现状、前沿热点和关键科学问题;(3)血管稳态与重构的调控机制研究面临的困难与挑战;(4)中国在血管病变相关重大疾病研究领域的主要方向.通过对血管生物医学领域具有普遍性、前沿性的重要科学问题进行讨论,提出阐明血管稳态和重构的调控机制是研究血管病变机制的关键.研究中应注重多学科交叉,利用基因组学、生物信息学、再生医学、影像学、组织工程与材料工程等领域的新进展,建立各种新方法、新技术和新的模式生物,为研究以血管病变为病理基础的多种重大疾病的机制、及实现早期预警和防治奠定基础.  相似文献   

11.
Endothelial injury related to oxidative stress is a key event in cardiovascular diseases, such as hypertension and atherosclerosis. The activation of the redox-sensitive Kv1.5 potassium channel mediates mitochondrial reactive oxygen species (ROS)-induced apoptosis in vascular smooth muscle cells and some cancer cells. Kv1.5 channel is therefore taken as a new potential therapeutic target for pulmonary hypertension and cancers. Although Kv1.5 is abundantly expressed in vascular endothelium, there is little knowledge of its role in endothelial injury related to oxidative stress. We found that DPO-1, a specific inhibitor of Kv1.5, attenuated H2O2-evoked endothelial cell apoptosis in an in vivo rat carotid arterial model. In human umbilical vein endothelial cells (HUVECs) and human pulmonary arterial endothelial cells (HPAECs), angiotensin II and oxLDL time- or concentration-dependently enhanced Kv1.5 protein expression in parallel with the production of intracellular ROS and endothelial cell injury. Moreover, siRNA-mediated knockdown of Kv1.5 attenuated, whereas adenovirus-mediated Kv1.5 cDNA overexpression enhanced oxLDL–induced cellular damage, NADPH oxidase and mitochondria-derived ROS production and restored the decrease in protein expression of mitochondria uncoupling protein 2 (UCP2). Collectively, these data suggest that Kv1.5 may play an important role in oxidative vascular endothelial injury.  相似文献   

12.
《Free radical research》2013,47(5):346-356
Abstract

Oxidative response regulates many physiological response in human health, but if not properly regulated it could also lead to a number of deleterious effects. The importance of oxidative stress injury depends on the molecular target, the severity of the stress, and the mechanism by which the oxidative stress is imposed: it has been implicated in several diseases including cancer, neurodegenerative diseases, malaria, rheumatoid arthritis and cardiovascular and kidney disease. Most of the common diseases, such as hypertension, atherosclerosis, heart failure, and renal dysfunction, are associated with vascular functional and structural alterations including endothelial dysfunction, altered contractility, and vascular remodeling. Common to these processes is increased bioavailability of reactive oxygen species (ROS), decreased nitric oxide (NO) levels, and reduced antioxidant capacity. Oxidative processes are up-regulated also in patients with chronic renal failure (CRF) and seem to be a cause of elevated risk of morbidity and mortality in these patients.

In this review, we highlight the role of oxidative stress in cardiovascular and renal disease.  相似文献   

13.
Reactive oxygen species in vascular biology: implications in hypertension   总被引:25,自引:1,他引:24  
Reactive oxygen species (ROS), including superoxide (·O2), hydrogen peroxide (H2O2), and hydroxyl anion (OH-), and reactive nitrogen species, such as nitric oxide (NO) and peroxynitrite (ONOO), are biologically important O2 derivatives that are increasingly recognized to be important in vascular biology through their oxidation/reduction (redox) potential. All vascular cell types (endothelial cells, vascular smooth muscle cells, and adventitial fibroblasts) produce ROS, primarily via cell membrane-associated NAD(P)H oxidase. Reactive oxygen species regulate vascular function by modulating cell growth, apoptosis/anoikis, migration, inflammation, secretion, and extracellular matrix protein production. An imbalance in redox state where pro-oxidants overwhelm anti-oxidant capacity results in oxidative stress. Oxidative stress and associated oxidative damage are mediators of vascular injury and inflammation in many cardiovascular diseases, including hypertension, hyperlipidemia, and diabetes. Increased generation of ROS has been demonstrated in experimental and human hypertension. Anti-oxidants and agents that interrupt NAD(P)H oxidase-driven ·O2 production regress vascular remodeling, improve endothelial function, reduce inflammation, and decrease blood pressure in hypertensive models. This experimental evidence has evoked considerable interest because of the possibilities that therapies targeted against reactive oxygen intermediates, by decreasing generation of ROS and/or by increasing availability of antioxidants, may be useful in minimizing vascular injury and hypertensive end organ damage. The present chapter focuses on the importance of ROS in vascular biology and discusses the role of oxidative stress in vascular damage in hypertension.  相似文献   

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15.
Vascular dysfunction associated with two-kidney, one-clip (2K-1C) hypertension may result from both altered matrix metalloproteinase (MMP) activity and higher concentrations of reactive oxygen species (ROS). Doxycycline is considering the most potent MMP inhibitor of tetracyclines and attenuates 2K-1C hypertension-induced high blood pressure and chronic vascular remodeling. Doxycycline might also act as a ROS scavenger and this may contribute to the amelioration of some cardiovascular diseases associated with increased concentrations of ROS. We hypothesized that in addition to its MMP inhibitory effect, doxycycline attenuates oxidative stress and improves nitric oxide (NO) bioavailability in 2K-1C hypertension, thus improving hypertension-induced arterial endothelial dysfunction. Sham operated or 2K-1C hypertensive rats were treated with doxycycline 30 mg/kg/day (or vehicle). After 8 weeks of treatment, aortic rings were isolated to assess endothelium dependent vasorelaxation to A23187. Arterial and systemic levels of ROS were respectively measured using dihydroethidine (DHE) and thiobarbituric acid reactive substances (TBARS). Neutrophils-derived ROS were tested in vitro using the fluoroprobe Carboxy-H(2)DCFDA and human neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA). NO levels were assessed in rat aortic endothelial cells by confocal microscopy. Aortic MMP activity was determined by in situ zymography. Doxycycline attenuated 2K-1C hypertension (169 ± 17.3 versus 209 ± 10.9mm Hg in hypertensive controls, p<0.05) and protected against hypertension-induced reduction in endothelium-dependent vasorelaxation to A23187 (p<0.05). Doxycycline also decreased hypertension-induced oxidative stress (p<0.05), higher MMP activity (p<0.01) and improved NO levels in aortic endothelial cells (p<0.01). Therefore, doxycycline ameliorates 2K-1C hypertension-induced endothelial dysfunction in aortas by inhibiting oxidative stress generation and improving NO bioavailability, in addition to its inhibitory effects on MMP activity.  相似文献   

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Several categories of chemotherapy confer substantial risk for late-term vascular morbidity and mortality. In the present study, we aimed to investigate the mechanism of acute chemotherapy-induced vascular injury in normal tissues. Specifically, we looked at activation of the acid sphingomyelinase (ASMase)/ceramide pathway, which leads to generation of reactive oxygen species (ROS) and induction of oxidative stress that may result in vascular injury.In particular, we focused on two distinct drugs, doxorubicin (DOX) and cisplatin (CIS) and their effects on normal endothelial cells. In vitro, DOX resulted in increased ASMase activity, intra-cellular ROS production and induction of apoptosis. CIS treatment generated significantly reduced effects in endothelial cells. In-vivo, murine femoral arterial blood flow was measured in real-time, during and after DOX or CIS administration, using fluorescence optical imaging system. While DOX caused constriction of small vessels and disintegration of large vessels' wall, CIS induced minor vascular changes in arterial blood flow, correlating with the in vitro findings. These results demonstrate that DOX induces acute vascular injury by increased ROS production, via activation of ASMase/ceramide pathway, while CIS increases ROS production and its immediate extracellular translocation, without causing detectable acute vascular injury. Our findings may potentially lead to the development of new strategies to prevent long-term cardiovascular morbidity in cancer survivors.  相似文献   

19.
Alzheimer’s disease (AD) and cerebrovascular diseases share common vascular risk factors that have disastrous effects on cerebrovascular regulation. Endothelial cells, lining inner walls of cerebral blood vessels, form a dynamic interface between the blood and the brain and are critical for the maintenance of neurovascular homeostasis. Accordingly, injury in endothelial cells is regarded as one of the earliest symptoms of impaired vasoregulatory mechanisms. Extracellular buildup of amyloid-β (Aβ) is a central pathogenic factor in AD. Aβ exerts potent detrimental effects on cerebral blood vessels and impairs endothelial structure and function. Recent evidence implicates vascular oxidative stress and activation of the non-selective cationic channel transient receptor potential melastatin (TRPM)-2 on endothelial cells in the mechanisms of Aβ-induced neurovascular dysfunction. Thus, Aβ triggers opening of TRPM2 channels in endothelial cells leading to intracellular Ca2+ overload and vasomotor dysfunction. The cerebrovascular dysfunction may contribute to AD pathogenesis by reducing the cerebral blood supply, leading to increased susceptibility to vascular insufficiency, and by promoting Aβ accumulation. The recent realization that vascular factors contribute to AD pathobiology suggests new targets for the prevention and treatment of this devastating disease.  相似文献   

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