炎症、氧化应激与阻塞性睡眠呼吸暂停低通气综合征

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是多种心脑血管疾病的独立危险因素。近年研究表明，睡眠时反复出现的呼吸暂停和低通气所致低氧可使体内产生过多的活性氧（ROS），后者是导致系统性炎症的一个重要原因。ROS是具有高度化学活性的分子或基团，不仅可以与核酸、脂质和蛋白质发生反应，进而妨碍细胞代谢、导致细胞损伤，还是引发高细胞因子血症的介质，并和炎症因子一起引起机体各种病理生理变化。近年来越来越多的证据表明，OSAHS患者体内存在氧化应激状态的改变和炎症因子的产生，这为深入认识OSAHS提出了一条新的思路。     

慢性脑低灌注致血管性痴呆发病机制研究进展

血管性痴呆（VaD）是一种神经退行性疾病,由整个大脑或局部大脑区域长期慢性低灌注引起,并最终发展为严重的认知功能障碍综合征。慢性脑低灌注可能是血脑屏障破坏、神经炎症、氧化应激、兴奋性毒性、神经血管解耦联、脱髓鞘和髓鞘再生失败等病理反应发生的基础,与VaD认知障碍的发生密切相关。慢性脑低灌注时血管内皮细胞功能障碍、周细胞丢失、血管周围空间增加导致血脑屏障分解和损伤,有害物质进入脑实质,造成白质病变、影响认知致VaD发生。慢性脑低灌注时促炎细胞因子过度激活,加剧神经炎症,诱发炎症—免疫级联反应,使白质损伤、神经元丢失,加速VaD发生发展。缺氧下内皮细胞中活性氧产生过量且细胞抗氧化系统无法对其适当调节,诱发氧化应激,损害内皮功能,加速神经血管功能障碍,导致白质损伤和认知损害。慢性脑低灌注时细胞能量失衡状态过度激活谷氨酸受体,使神经元功能紊乱和死亡,出现兴奋性毒性,导致细胞凋亡或坏死,最终诱发VaD。大脑能量供应紊乱、神经血管单元之间的细胞信号转导和营养耦合发生异常,使神经血管单元功能整体损害,导致一系列级联反应诱发VaD。慢性脑低灌注时少突胶质细胞祖细胞易损伤而发育停滞,致髓鞘再生失败,兴奋...     

阻塞性睡眠呼吸暂停低通气综合征致心血管损害机制的研究进展

阻塞性睡眠呼吸暂停低通气综合征(obstructive sleepapnea hypopnea syndrome,OSAHS)患者反复发生的低氧、复氧和睡眠结构的紊乱对人体各项生理功能产生重大影响,特别是对心血管系统的损伤,涉及氧化应激及炎症机制、交     

间歇低氧与系统性炎症

OSAHs的特点为低氧与正常氧频繁交替,属于间歇低氧,或准确地称为睡眠呼吸暂停模式间歇低氧.这种低氧模式下,人、实验动物及细胞均表现出多种炎性因子水平增高,产生炎症反应和损伤.近期研究结果证实,间歇低氧与炎症之间不但关联,而且存在因果关系.这种炎症发生在局部,但遍布全身,故称为系统性炎症,与OSAHS的多器官损害,特别是内皮功能障碍、动脉粥样硬化和心脑血管合并症密切相关.     

慢性间歇低氧对小鼠海马CA1区神经元自噬的影响

OSAHS是一种常见的睡眠呼吸障碍性疾病,以睡眠过程中反复出现的呼吸暂停为特点,慢性间歇低氧(chronic intermittent hypoxia,CIH)被认为是OSAHS发病环节中最主要的病理生理机制[1] ,其与氧化应激、炎症反应、细胞凋亡的关系已有不少报道[2].     

糖尿病视网膜病变患者神经血管单元损伤的机制研究进展

糖尿病视网膜病（DR）是一种高度组织特异性的神经血管并发症，视网膜神经血管单元（NVU）正常结构及功能受损直接介导DR的病程进展。在糖尿病状态下，Müller细胞功能障碍，使谷氨酸浓度增加，出现谷氨酸兴奋性毒性，导致视网膜神经元不可逆损伤；氧化应激介导神经胶质细胞异常分泌众多炎症因子，使视网膜长期处于炎症状态，诱发视网膜神经细胞凋亡和微血管病变；视网膜神经保护因子失衡会打破视网膜内环境稳定，致使视网膜神经变性，诱导早期微血管病变；长期高糖亦能引起视网膜局部微血管异常，与视网膜神经变性相互影响，最终加重视网膜NVU破坏，造成不可逆的DR。针对NVU损伤这一DR早期事件，及早干预、采取有效防治措施有望降低DR发病风险。     

阻塞性睡眠呼吸暂停低通气综合征患者认知功能障碍的相关研究进展

正阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)的特点是夜间睡眠期间长期反复发生上气道塌陷而导致的呼吸暂停和/或低通气,引起慢性间歇性低氧(chronic intermittent hypoxia,CIH)和睡眠呼吸结构紊乱[1]。OSAHS可导致心血管、神经、内分泌、代谢等全身各个系统及器官损害。OSAHS引起的认知功能障碍一般认为是轻度认知功能障碍(mild cognitive impairment,     

星形胶质细胞与阿尔茨海默病

阿尔茨海默病是老年人的常见病和多发病,它的发生,发展与包括星形胶质细胞在内的多种因素有关。近年来的研究发现,星形胶质细胞在阿尔茨海默病发病的早期被激活,增生并释放多种炎症细胞因子（IL－1,IL－6,INF等）和促生长因子S100以及诱导iNOS表达,在脑内开成反复的神经免疫反应和病理改变,导致神经毒性的β－淀粉样蛋白沉积加速,神经纤维缠结形成,神经元损伤及丢失。     

小胶质细胞在帕金森病发病学中的作用

帕金森病是仅次于阿尔茨海默病的神经系统退行性疾病。其发病原因尚未明确。目前越来越多的研究关注小胶质细胞激活在帕金森病发病学中的作用。多种原因激活小胶质细胞后．通过炎症反应和氧化应激机制引起黑质多巴胺能神经元死亡。美满霉素、地塞米松、纳洛酮、水飞藜素以及COX-2抑制剂等可以抑制小胶质细胞的激活，保护多巴胺能神经元免受氧化应激损伤，此类抑制小胶质细胞激活的药物有可能成为帕金森病神经保护的有效药物。     

睡眠呼吸暂停综合征对机体的影响

一、1概述 睡眠呼吸暂停综合征（sleep apnea syndrome SAS）是指各种原因导致睡眠状态下反复出现呼吸暂停,引起低氧血症、高碳酸血症、睡眠中断,从而使机体发生一系列病理生理改变的临床综合征。基本指标是每晚睡眠过程中呼吸暂停反复发作30次以上或睡眠呼吸暂停低通气指数（apnea hypopnea index，AHI）≥5次／h并伴有嗜睡等临床症状；呼吸暂停是指睡眠过程中口鼻呼吸气流完全停止10s以上。     

阻塞性睡眠呼吸暂停导致认知功能障碍的机制及与孤束核病变的关系

阻塞性睡眠呼吸暂停（OSA）是近年来较为常见的一种疾病,可以引起多系统病变.OSA导致的认知功能障碍也越来越受到重视.低氧血症和睡眠结构紊乱诱导的氧化应激和炎症反应等被认为是OSA患者发生认知功能障碍的主要机制.目前一个新的假说强调,在OSA的患者中孤束核的炎症和结构异常在触发记忆和认知功能障碍亦可能发挥举足轻重的作用.因此,进一步研究OSA导致认知功能障碍的病理机制及与孤束核病变的关系,将为OSA患者并发认知功能障碍的防治提供一新视角.     

实验性阻塞型睡眠呼吸暂停综合征小型猪的氧化应激反应

目的利用动物模型观察实验型阻塞型睡眠呼吸暂停综合征小型猪的氧化应激反应,以探讨睡眠呼吸暂停致动脉粥样硬化的可能机制。方法中国小型猪16头,分为阻塞型睡眠呼吸暂停（OSA）组和对照组,每组8头。OSA组用凝胶注射法制作动物模型。分别于制作模型前及12周后取实验动物静脉血检测黄嘌呤氧化酶（XOD）、超氧化物岐化酶（SOD）及丙二醛（MDA）。结果（1）实验后,OSA组XOD水平明显升高,前后分别为（3．71土0．07）U／L和（4．82±0．08）U／L,两者相比差异有统计学意义,对照组XOD水平无明显变化。实验后OSA组与对照组XOD值相比差异有统计学意义。（2）实验后,OSA组的SOD水平明显降低,前后分别为（142．33±6．82）NU／ml和（121．21士1．93）NU／ml,两者相比差异有统计学意义;MDA水平明显升高,前后分别为（3．66±0．47）μmol／L和（5．59士0．75）μmol／L,两者相比差异有统计学意义。对照组SOD水平及MDA水平无明显变化,实验后OSA组与对照组二指标相比差异有统计学意义（P〈0．05）。结论实验性阻塞型睡眠呼吸暂停使动物机体处于氧化应激状态,产生了大量的氧自由基,增多的氧自由基介导了一系列病理生理反应,促进了动脉粥样硬化的发生和发展。     

Melatonin ameliorates endothelial dysfunction,vascular inflammation,and systemic hypertension in rats with chronic intermittent hypoxia

The pathogenesis of hypertension in patients with obstructive sleep apnea (OSA) is associated with endothelial dysfunction induced by chronic intermittent hypoxia (IH). Studies have shown that administration of melatonin ameliorates oxidative injury and inflammation. This study examined the effect of melatonin on the oxidative stress, endothelial dysfunction, and inflammation during the pathogenesis of hypertension in chronic IH. Adult Sprague‐Dawley rats that had received a daily injection of melatonin or vehicle were exposed to IH treatment mimicking a severe OSA condition for 14–21 days. Systolic pressure was significantly higher in the vehicle‐treated (144 ± 2.7 mmHg) but not in the melatonin‐treated rats (123 ± 5.1 mmHg) by 21–day IH treatment when compared with the normoxic control. Levels of malondialdehyde and the expressions of NADPH oxidase, pro‐inflammatory mediators (TNF‐α, inducible NO synthase, COX‐2), and adhesion molecules (ICAM‐1, VCAM‐1, and E‐selectin) of the thoracic aorta were markedly increased by 14‐day IH treatment preceding the hypertensive response. Also, levels of nitric oxide (NO˙), endothelial‐dependent relaxation, and the expressions of endothelial NO synthase (eNOS) and antioxidant enzymes (GPx, CAT, and Cu/Zn SOD) were significantly lowered in the IH rats. Melatonin treatment significantly mitigated the increased expression of NADPH oxidase, pro‐inflammatory mediators, and adhesion molecules. Moreover, melatonin prevented the endothelial dysfunction with ameliorated levels of NO˙, endothelial‐dependent relaxation, and expressions of eNOS and antioxidant enzymes. These results suggest that melatonin is protective against IH‐induced hypertension and endothelial dysfunction via an antioxidant and anti‐inflammatory mechanism.     

Obstructive sleep apnea: the new cardiovascular disease. Part I: obstructive sleep apnea and the pathogenesis of vascular disease

Obstructive sleep apnea (OSA) is increasingly recognized as a novel cardiovascular risk factor. OSA is implicated in the pathogenesis of hypertension, left ventricular dysfunction, coronary artery disease and stroke. OSA exerts its negative cardiovascular consequences through its unique pattern of intermittent hypoxia. Endothelial dysfunction, oxidative stress, and inflammation are all consequences of OSA directly linked to intermittent hypoxia and critical pathways in the pathogenesis of cardiovascular disease in patients with OSA. This review will discuss the known mechanisms of vascular dysfunction in patients with OSA and their implications for cardiovascular disease.     

Metabolic consequences of intermittent hypoxia: relevance to obstructive sleep apnea

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia (IH) during sleep. There is growing evidence from animal models of OSA that IH is independently associated with metabolic dysfunction, including dyslipidemia and insulin resistance. The precise mechanisms by which IH induces metabolic disturbances are not fully understood. Over the last decade, several groups of investigators developed a rodent model of IH, which emulates the oxyhemoglobin profile in human OSA. In the mouse model, IH induces dyslipidemia, insulin resistance and pancreatic endocrine dysfunction, similar to those observed in human OSA. Recent reports provided new insights in possible mechanisms by which IH affects lipid and glucose metabolism. IH may induce dyslipidemia by up-regulating lipid biosynthesis in the liver, increasing adipose tissue lipolysis with subsequent free fatty acid flux to the liver, and inhibiting lipoprotein clearance. IH may affect glucose metabolism by inducing sympathetic activation, increasing systemic inflammation, increasing counter-regulatory hormones and fatty acids, and causing direct pancreatic beta-cell injury. IH models of OSA have improved our understanding of the metabolic impact of OSA, but further studies are needed before we can translate recent basic research findings to clinical practice.     

中性粒细胞凋亡延迟与重叠综合征患者的氧化应激和系统性炎症

呼吸重叠综合征简称重叠综合征（OS）通常是指阻塞性睡眠呼吸暂停（OSA）和COPD的共患,其较单纯COPD或OSA存在更明显的低氧血症的发生,并且心血管并发症的发生率和病死率也明显增加。本文综述了OS导致氧化应激和系统性炎症的可能机制以及中性粒细胞凋亡延迟相关的调节机制。     

阻塞性睡眠呼吸暂停低通气综合征与高血压的研究进展

阻塞性睡眠呼吸暂停低通气综合征（obstructive sleep apnea hyponea syndrome,OSAHS）是指在睡眠过程中上呼吸道塌陷阻塞引起的呼吸暂停和通气不足,伴有打鼾、睡眠结构紊乱、频繁发生血氧饱和度下降及白天嗜睡等病理综合征。OSAHS与高血压病关系密切,OSAHS是高血压独立危险因素之一,可通过导致血管内皮功能障碍,激活交感神经系统和肾素一血管紧张素一醛固酮系统,促进脂质代谢障碍及增加氧化应激等途径介导高血压病的发生、发展。现就目前OSAHS与高血压研究新进展做一综述。     

Obstructive sleep apnea and multiple facets of a neuroinflammatory response: a narrative review

BackgroundObstructive sleep apnea (OSA) is a chronic, highly prevalent, multi-system and sleep disorder, which may contribute to cognitive impairment and a variety of structural and neurophysiologic changes. The focus on OSA is warranted given its recognized links with major psychiatric and neurologic disorders, including Alzheimer’s disease. Some preliminary studies suggest a dual effect of the inflammatory response in OSA. Neuroinflammation may present with initial, potentially adaptive and homeostatic, and later, a more distinctly maladaptive, precipitating and perpetuating role.ObjectiveWe here propose and argue in favour of the inflammatory process in the brain as a likely binding mechanism behind at least some effects that OSA may have on the brain and its function. Several OSA-triggered molecular and cellular events, that could lead to a neurodegenerative cascade, are similarly discussed.MethodsThis perspective reviews the body of literature that investigates potential links between the inflammatory processes in the brain and the OSA. A special emphasis is placed on a potential role for neuroplastin, a novel transmembrane synaptic protein involved in the neuroplasticity and known to be differentially regulated in the OSA.ConclusionsThe intricate interplay between neuroinflammation and other mechanistic correlates of OSA add to the evidence that neuroinflammation may be a key target for future therapeutic strategies in a number of comorbid disorders. The future studies will need to answer whether it is sleep fragmentation (SF) or intermittent hypoxia (IH) which may drive any such neuroinflammation.     

Endothelial mechanisms of endothelial dysfunction in patients with obstructive sleep apnea

Background  

Obstructive sleep apnea (OSA) occurs in 2% of middle-aged women and 4% of middle-aged men in the general population and the prevalence is much higher in specific patient groups. Intermittent hypoxia (IH, oxygen desaturation and re-oxygenation) cycle, a major pathophysiologic character of OSA, and the physiological responses this evokes are thought to be responsible for its association with increased cardiovascular morbidity and mortality. Endothelial dysfunction, resulting from IH and as a key early event in atherosclerosis, was demonstrated repeatedly in patients with OSA and in animal models of IH, providing an important mechanistic link between the acute cyclical IH during sleep and the increased prevalence of chronic vascular diseases.     

Vascular changes, cardiovascular disease and obstructive sleep apnea

Vascular changes related to obstructive sleep apnea (OSA) can lead to chronic cardiovascular consequences such as hypertension. The cardiovascular consequences are owing to nocturnal perturbations related to intrathoracic pressure changes, intermittent hypoxia, sympathetic neural activation, endothelial dysfunction, oxidative stress and systemic inflammation. Intermittent hypoxia due to sleep-related events in OSA activates the renin-angiotensin system and increases the levels of endothelin-1. Intermittent hypoxia also results in oxidative stress, as evidenced by elevated levels of xanthine oxidoreductase, lipid peroxidation and the presence of reactive oxygen species. There is also evidence for a decrease in antioxidant capacity. Patients with OSA may have endothelial dysfunction that resolves with continuous positive airway pressure. OSA is a state of inflammation as evidenced by elevated levels of C-reactive protein, IL-6, NF-κB, TNF-α, ICAM-1, VCAM-1 and E-selectin. This may suggest that OSA is a predisposing factor for atherogenesis. This article will discuss the role of nocturnal perturbations consequent to OSA resulting in endothelial dysfunction, oxidative stress, and inflammation and how they may subsequently play a causative role in cardiovascular disorders.