间歇低氧对大鼠血管内皮硫氧还蛋白的影响

目的 通过测定睡眠呼吸暂停模式间歇低氧大鼠血管内皮硫氧还蛋白(thioredoxin,TRX)mRNA的表达水平,进一步探讨氧化应激在阻塞性睡眠呼吸暂停综合征导致高血压发生机制中的具体作用.方法 160只成年雄性Wistar大鼠随机分为5组:5%间歇低氧组,7.5%间歇低氧组,10%间歇低氧组,10%持续低氧对照组和常...     

不同程度间歇低氧大鼠血清丙二醛含量、超氧化物歧化酶和谷胱甘肽过氧化物酶活性的变化

目的 通过测定不同程度间歇低氧大鼠血清丙二醛(MDA)含量及部分抗氧化酶的活性,以探讨氧化应激与阻塞性睡眠呼吸暂停模式间歇低氧的关系,为进一步研究阻塞性睡眠呼吸暂停综合征所致心血管并发症的发病机制提供研究基础.方法 160只成年雄性Wistar大鼠随机均分为5组:5%间歇低氧组、7.5%间歇低氧组、10%间歇低氧组、10%持续低氧对照组和常氧对照组.分别于2周、4周、6周、8周测定各组大鼠血清MDA含量、超氧化物歧化酶(SOD)活性和谷胱甘肽过氧化物酶(GPx)活性.结果 间歇低氧暴露后大鼠血清MDA含量升高,而且间歇低氧程度不同,MDA含量升高的程度不同,5%间歇低氧组MDA含量升高最为明显;间歇低氧暴露后血清SOD和GPx活性降低,暴露6周时变化最为明显.结论 阻塞性睡眠呼吸暂停模式间歇低氧能引起机体发生氧化应激反应,间歇低氧程度不同,所引起的氧化应激反应强度不同,重度间歇低氧引起的氧化应激反应最为明显.     

不同程度慢性间歇低氧对大鼠神经细胞凋亡的影响

目的观察不同程度、时限的间歇低氧大鼠神经细胞凋亡情况,探讨阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者神经系统损伤的机制。方法将72只Wistar大鼠均分为3组：5%慢性间歇低氧组（CIH5%组）、10%慢性间歇性低氧组（CIH10%组）和空白对照组（UC组）。TUNEL法观察大鼠神经细胞凋亡情况,HE染色观察神经细胞形态变化。结果与UC组比较,CIH5%组和CIH10%组皮质和海马等部位神经细胞出现损伤,神经细胞凋亡指数升高,6周时达到高峰,CIH5%组较CIH10%组变化明显。结论慢性间歇低氧可引起神经细胞凋亡,其程度与间歇低氧程度有关,但延长间歇低氧时间未加重神经细胞凋亡。     

慢性间歇低氧并高血压SD大鼠模型的建立

目的建立慢性间歇低氧并高血压SD大鼠模型,为研究阻塞性睡眠呼吸暂停低通气综合征(OSAHS)并高血压的发病机制提供简单可复制的动物模型。方法氧舱系统分为控制系统、气源系统、暴露舱三个部分。选8~10周龄SD雄性大鼠24只(200~250 g)随机分成间歇低氧干预组和对照组。间歇低氧干预组12只暴露于间歇低氧舱内,白天给予间歇低氧干预(6%~8%的O_2 40 s/21%的O_2 80 s,如此往复循环8 h);对照组12只暴露于常氧舱。在安静状态下检测大鼠尾动脉收缩压,每只连续测量3次,取平均值。结果实验第35天,间歇低氧干预组尾动脉收缩压[(136.21±32.46)mmHg]高于对照组[(121.37±35.37)mmHg](P0.05)。结论控制精确气源通断时间,可有效地模拟间歇低氧过程,重复性佳,是研究间歇低氧所致高血压机制的理想实验模型。     

交感神经兴奋在慢性间歇性低氧引起高血压发生过程中的作用

交感神经活性增强在阻塞性睡眠呼吸暂停引起的高血压及其他心血管疾病发生过程中起到重要作用.阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)最为明显的特征就是夜间反复的间歇 性低氧,这种间歇性低氧状态对于交感神经激活及血压升高显得尤为重要.以下就OSA相关性间歇性低氧引起的交感神经系统激活以及其...     

睡眠呼吸暂停低通气或间歇低氧与高血压

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是发病率较高、合并症较多的睡眠呼吸疾患。众多的临床和流行病学研究结果表明，OSAHS是高血压发病的独立危险因素^[1]，其机制尚未完全阐明。患者睡眠中因呼吸暂停引起的反复短暂缺氧为间歇低氧（intermittenthypoxia），这是OSAHS的主要病理生理学特点和损伤机制。近年来越来越多的研究结果显示，间歇低氧与OSAHS患者高血压的发生密切相关。     

模拟慢性间歇低氧对大鼠左心室心肌力学的影响

睡眠期间反复短暂缺氧是阻塞性睡眠呼吸暂停低通气综合征 (OSAHS)患者的主要发病特点。我们模拟OSAHS患者的低氧特点 ,观察慢性间歇低氧对大鼠左心室功能的影响。材料与方法　雄性Wistar大鼠 30只 (中国军事医学科学院实验动物所提供 ) ,体重 2 5 0～ 30 0g ,采用随机排列表法分为间歇低氧组 (IH组 )、实验对照组 (SC组 )和空白对照组(UC组 ) ,每组 10只。将IH组和SC组的大鼠分别置于 2个相同的有机玻璃舱内 ,每天 8h ,共 6周。IH组的舱内循环充入氮气和压缩空气 ,每一循环 6 0s,即 30s充入氮气 ,随之 30s充入压缩空气 ,并调节气…     

阻塞性睡眠呼吸暂停低通气综合征患者夜间多尿发病机制的研究进展

阻塞性睡眠呼吸暂停低通气综合征是指睡眠过程中上气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、白天嗜睡等病征,也可出现睡眠时异常行为,如梦游、遗尿、肌阵挛、夜尿症等现象.其中夜尿增多是最常见的症状之一,但机制尚不明确,间歇低氧所致肾功能改变或体液因子异常可能是阻塞性睡眠呼吸暂停低通气综合征患者夜尿增多的原因.     

慢性间歇低氧与氧化应激

慢性间歇低氧(Chronic intermittent hypoxia,CIH)是睡眠呼吸暂停的重要病理生理机制,是造成OSAHS患者心血管系统以及其他脏器损害的基础.与广义的间歇低氧不同,睡眠呼吸暂停模式的CIH具有如下特点:正常氧和低氧交替出现,不管低氧程度多么严重,低氧解除后都会恢复到正常氧水平.低氧发生的频率很高,一般在5～100次/h,平均每1～5 min发生1次.低氧程度严重,血氧变化幅度大,最低动脉氧饱和度可降低到20%或更低,正常氧与低氧间动脉血氧饱和度之差可达30%～70%[1].此过程类似缺血再灌注损伤,可引起氧化应激反应,成为睡眠呼吸暂停靶器官损伤的重要机制.     

阻塞性睡眠呼吸暂停与癌症相关研究进展

阻塞性睡眠呼吸暂停(OSA)和癌症都是常见疾病。睡眠呼吸暂停发作时可伴有间歇低氧。研究表明, OSA的间歇性低氧可能影响肿瘤的发生, 而OSA与癌症的关系目前仍没有完全研究清楚, 阐明这个问题需要动物和细胞模型方面的实验以及人群的流行病学研究。该文就OSA与癌症相关的流行病学、病理生理、治疗进展等作一综述, 试图阐述OSA和癌症的关系。     

不同频率间歇低氧下大鼠肝脏氧化应激损伤及Tempol的干预作用

目的 探讨不同频率间歇低氧(IH)对大鼠肝脏氧化应激损伤差异和Tempol的干预作用及可能机制.方法 应用慢性间歇低氧(CIH)大鼠模型,模拟OSAS周期性间歇低氧/再氧和病理生理过程.56只雄性Wistar大鼠随机分为不同频率IH组(IH1,IH2,IH3,IH4,频率依次为10、20、30、40次/h),30T组(...     

Antioxidant vitamins prevent oxidative and carbonyl stress in an animal model of obstructive sleep apnea

Purpose

The aim of our study was to analyze the effects of an antioxidant treatment on markers of oxidative and carbonyl stress in a rat model of obstructive sleep apnea.

Methods

Wistar rats were randomized into six groups—according to gender and intervention—sham, intermittent hypoxia, and intermittent hypoxia with treatment by vitamins C and E. Rats underwent tracheostomy. The tracheal cannula was closed for 12 s every minute for 1 h to simulate obstructive sleep apnea-related intermittent hypoxia. In the treatment group, rats received vitamin C and E 24 h prior to surgery.

Results

The intervention had a significant effect on advanced oxidation protein products (p?=?0.008) and advanced glycation end products–specific fluorescence (p?=?0.006) but no effect on malondialdehyde. Oxidation and glycation protein products were higher in intermittent hypoxia groups than in sham and in treated groups.

Conclusions

Antioxidants alleviate oxidative and carbonyl stress in an experimental model of obstructive sleep apnea. Future studies will show whether such treatment has any clinical value regarding cardiovascular complications of sleep apnea syndrome, preferably in patients with low compliance to continuous positive airway pressure.     

Effects of various degrees of oxidative stress induced by intermittent hypoxia in rat myocardial tissues

Background and objective: The aim of this study was to investigate the mechanism by which oxidative stress induced by chronic intermittent hypoxia (IH) causes myocardial damage in obstructive sleep apnoea syndrome. Methods: A total of 160 Wistar rats were divided into five experimental groups and subjected to chronic IH with different concentrations of oxygen (5%, 7.5%, 10% IH groups; 10% continuous oxygen and normoxia control groups). Eight rats from each group were sacrificed at the 2‐, 4‐, 6‐ and 8‐week time points. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels and total anti‐oxidant capability (T‐AOC) were measured in supernatants of heart homogenates. Expression of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22^phox and NOX2, and thioredoxin‐2 (Trx‐2) genes were determined by measuring messenger RNA (mRNA) levels by real‐time polymerase chain reaction. Results: Compared with the control groups, MDA levels increased over time in the IH groups, whereas T‐AOC and SOD activity decreased over time. MDA, T‐AOC and SOD activity peaked at 6 weeks into the IH treatment. The 5% IH group showed significantly higher expression of p22^phox and thioredoxin‐2 mRNA, as compared with the other IH groups, as well as the control groups. Conclusions: The severity of oxidative stress induced by chronic IH in myocardial tissue was significantly correlated with the degree of IH. NADPH oxidase and Trx‐2 are important mediators of oxidative stress induced by IH.     

间歇缺氧大鼠海马神经元凋亡及其机制

目的探讨间歇缺氧对大鼠海马组织氧化应激状态及海马神经元凋亡的影响及其可能的机制。方法将36只雄性Wistar大鼠随机分为间歇缺氧组、持续缺氧组和正常对照组，每组12只。采用化学比色法测定海马组织丙二醛和超氧化物歧化酶（SOD）水平，应用Western免疫印迹法检测海马CA1区磷酸化C—JUN氨基末端激酶（p-JNK）、磷酸化c-jun（p-c-jun）的表达水平，应用缺口末端标记（TUNEL）法检测海马CA1区神经元凋亡率。结果间歇缺氧组大鼠海马CAl区丙二醛水平为（1．61±0．39）nmol／mg蛋白，显著高于正常对照组的[（1．25±0．29）nmol／mg蛋白]和持续缺氧组的[（1．34±0．24）nmol／mg蛋白]；间歇缺氧组大鼠海马CAl区SOD水平为（45±13）NU／mg蛋白，显著低于正常对照组[（58±12）NU／mg蛋白]和持续缺氧组[（56±10）NU／mg蛋白]；持续缺氧组与正常对照组的差异均无统计学意义。间歇缺氧组p-JNK、p—c-jun表达显著增高，分别是正常对照组的2．1倍及2．3倍；间歇缺氧组海马CA1区神经元凋亡率为（0．30±0．16）％，显著高于正常对照组[（0．12±0．07）％]和持续缺氧组[（0．17±0．09）]。结论间歇缺氧可导致海马CA1区氧化应激状态，从而激活JNK信号传导通路，介导海马神经元凋亡，这可能是阻塞性睡眠呼吸暂停低通气综合征患者神经功能障碍的病理生理基础之一。【     

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。     

间歇低氧程度与频率对血管内皮细胞超氧化物歧化酶和丙二醛分泌水平的影响

目的 探讨不同程度和频率间歇低氧对人血管内皮细胞超氧化物歧化酶(SOD)和丙二醛(MDA)分泌水平的影响.方法 采用人脐静脉内皮细胞(ECV304细胞株)建立细胞模型.实验细胞株分为间歇正常氧组和间歇低氧(IH)组,根据低氧程度设立3个亚组:轻度低氧组、中度低氧组和重度低氧组,根据低氧频率不同设立5个亚组.分别以不同程度和不同频率间歇低氧环境暴露细胞,采用酶联免疫法测定细胞胚基中SOD和MDA水平.结果 不同程度间歇低氧组中MDA水平均高于间歇正常氧组(P＜0.01),随低氧程度增加呈逐渐升高(P＜0.01).SOD水平在3个不同程度IH组均低于间歇正常氧组(P＜0.01),SOD随IH程度减低逐渐下降(P＜0.01).SOD水平在IH频率为40和20次/h之间差异无统计学意义(P＞0.05),随IH频率降低,SOD水平逐渐降低,至9.2次/h达到最高,至6.3次/h再次下降(P＜0.01).MDA水平在IH频率为40次/h与20次/h间差异无统计学意义(P＞0.05),之后随IH频率降低,MDA水平逐渐升高,至9.2次/h达到最低,至6.3次/h再次轻度上升(P＜0.01).正常氧与3个不同程度IH组,SOD与MDA均值呈负相关(r=0.932,P＜0.01).不同频率IH暴露,5个不同频率IH组SOD与MDA均值呈负相关(r=0.832,P＜0.01).结论 间歇低氧暴露人脐动脉内皮细胞氧化应激反应增强,抗氧化能力减低,其减低和增高具有低氧程度依赖性.不同频率间歇低氧暴露,脐动脉上皮细胞氧化应激反应增强,抗氧化能力减低随频率减低逐渐增强和减低的趋势.低氧程度对氧化应激反应的影响高于频率,间歇低氧暴露上皮细胞出现氧化和抗氧化平衡的失调.

Abstract：

Objective To investigate the effect of different degrees and frequencies of intermittent hypoxia on levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in vascular endothelial cells.Methods Umbilical vein endothelial cell ECV304 was used to set up the cell model.The experiment consisted of 1 control group(normal air)and 8 experimental groups,in which the cells were exposed to 3 different degrees and 5 different frequencies of intermittent hypoxia.The levels of SOD and MDA were measured by ELISA in cytoblastema.ResulIs The levels of MDA in the 3 different degree intermittent hypoxia groups were higher than that in the control group(P＜0.01)The levels of SOD in the 3 different degree hypoxia groups were lower than that in the control group(P＜0.01).The level of SOD decreased and the level of MDA increased with decreasing degrees of hypoxia(P＜0.01).The level of MDA was not different between the groups with hypoxia for 40 times/h and 20 times/h(P＞0.05).With decreased hypoxia frequency,the level of MDA increased;the MDA level of the 9.2 times/h subgroup was the lowest, but the level of MDA increased slightly when the frequency reached 6.3 times/h(P＜0.01).When hypoxia frequency decreased.the level of SOD decreased,and the level of the 9.2 times/h group was the highest,but the level of SOD decreased again when the hypoxia frequency reached 6.3 times/h(P＜0.01).The level of SOD was negatively correlated to that of MDA under different degrees of hypoxia exposure(r= 0.932,P＜0.01).and the level of SOD was negatively correlated to that of MDA under difierent frequencies of exposure(r=0.832,P＜0.01).Conclusion Intermittent hypoxia activates oxidative stress in endothelial cells,leading to increase of reactive oxygen species,with the antioxidant capacity impaired.The decrease and increase of oxidative stress reaction depended on the degree of hypoxia and were correlated to the frequency of hypoxia.With exposure to intermittent hypoxia,the balalice between oxidative stress and antioxidative system in endothelial cells was disturbed.     

重度间歇低氧大鼠学习记忆功能与氧化应激的关系

目的 通过建立重度间歇低氧动物模型,探讨OSAHS大鼠学习记忆功能与氧化应激的关系.方法 成年雄性Wistar大鼠48只,体重(170±10)g,采用随机数字法分为5％间歇性低氧组和对照组,每组又分为2、4、6和8周时间组,每组6只,其中实验组给予5％间歇低氧,并分别在2、4、6、8周进行Morris水迷宫检测学习记忆功能,随后处死大鼠,取脑组织于透射电子显微镜下观察海马区超微结构的变化,通过化学比色法测定海马组织超氧化物歧化酶(SOD)活性和丙二醛水平.结果 与对照组比较,实验组大鼠水迷宫测试大鼠逃避潜伏期时间延长、跨越目标象限时间缩短、穿台次数减少,与对照组相比差异具有统计学意义(P＜0.05);随着间歇低氧持续时间延长,实验组各时间点学习功能的改变差异组间比较差异均有统计学意义(均P＜0.05).对照组大鼠海马组织于电子显微镜下神经元结构完整,细胞器丰富,而实验组大鼠海马组织的神经元和突触数量明显减少,细胞核皱缩,突触结构模糊,突触间隙增宽,且随着暴露时间的延长,细胞损伤改变愈加明显.与对照组比较,实验组海马组织丙二醛含量明显增高,而SOD活性降低,且随间歇低氧时间延长其变化更为明显,差异有统计学意义(均P＜0.05).结论 间歇重度低氧大鼠海马组织存在氧化应激损伤,可能通过引起神经元及突触数量与结构的改变,从而导致学习记忆功能障碍,且随着缺氧时间的延长逐渐加重.     

Long-term intermittent hypoxia: reduced excitatory hypoglossal nerve output

Humans with long-standing sleep apnea show mixed responses to serotonergic therapies for obstructive sleep apnea. We hypothesize that long-term intermittent hypoxia may result in oxidative injury to upper airway motoneurons, thereby diminishing serotonergic motoneuronal excitation. Unilateral serotonin and glutamate agonist and antagonist microinjections into the hypoglossal motor nuclei in adult rats exposed to 3 weeks of intermittent hypoxia showed reduced hypoglossal nerve responsiveness (logEC50) for serotonin and N-methyl-D-aspartate. However, long-term intermittent hypoxia did not appear to alter hypoglossal response to alpha-amino-3-hydroxy-methylisoxazole-4-propionic acid injections. There was no reduction in hypoglossal motoneuron soma number or in serotonergic postsynaptic receptor mRNA copy numbers within single-cells; in contrast, there was an increase in isoprostanes in the dorsal medulla. Systemic 4-hydroxyl-2,2,6,6-tetramethylpiperidin-1-oxyl (tempol) throughout exposure to intermittent hypoxia improved the EC50 for serotonin to a larger extent than glutamate and normalized medullary isoprostanes. Protein kinase C activity within the hypoglossal nucleus was increased after long-term intermittent hypoxia. These results suggest that long-term intermittent hypoxia reduces serotonergic and N-methyl-D-aspartate excitatory output of hypoglossal nerves, and that reduced excitatory responsiveness and lipid peroxidation are largely prevented with superoxide dismutase treatment throughout hypoxia/reoxygenation. Similar alterations in neurochemical responsiveness may occur in select persons with obstructive sleep apnea.