低氧诱导因子1研究进展

机体或细胞在低氧环境中可产生低氧诱导因子１（ＨＩＦ１）及多种类分子,通过转录水平参与对低氧反应性基因的调控,从而使机体或细胞进一步对低氧刺激作出复杂的病理生理性反应。其详细的生物学功能及具体的调节机制等问题还尚待研究     

低氧对细胞的影响及其适应机制

低氧(hypoxia)损伤是临床许多疾病中常见的病理过程,也是导致机体死亡的重要原因之一.随着分子生物学和细胞检测技术的快速发展,人们对细胞低氧损伤及其适应机制的研究日益深入.低氧作为细胞生长潜在的环境致死因素,影响着细胞周期、形态结构、代谢、信号通路、增殖、分化及凋亡等多个方面.另一方面,低氧又还是癌细胞转移及产生耐药的原因之一.机体细胞为适应低氧环境以减少损伤,诱导产生的低氧诱导因子(hypoxia-inducible factor,HIF)是低氧应答时基因表达和恢复细胞内环境稳定的中心调控因子;此外,nonsense mediated RNA的衰变、microRNA的诱导、染色质的核型改变和翻译调节等也是细胞对低氧的适应途径.阐明细胞低氧损伤及其适应机制具有重要意义,也可以为相关疾病的治疗提供新思路.     

脑低氧／缺血性预适应的机制

氧是维持生命活动必不可少的物质。由于各种原因导致机体氧供不足及／或机体氧利用障碍，皆可导致缺氧或低氧性病理过程，缺氧或低氧性心脑肺疾患尤为常见。研究和克服缺氧既是临床医学、也是航空航天医学、高原医学以及运动医学等面临的重大课题。克服与战胜缺氧的一个主要策略是对之进行服习或适应。人或动物通过间断或连续地处于高原或低氧环境，可以产生或形成对缺氧的适应。事先短暂的缺血或轻度低氧的重复预处理或预适应（preconditioning）亦可触发或动员机体内在的防护能力，从而对随后的严重缺氧或缺血损伤产生强大的防御和保护作…     

高原习服与低氧预适应

高原低氧易导致急性高原反应,高原习服是机体为适应高原低氧环境发生的一系列代偿适应性变化。寻找加快高原习服的有效措施,提高机体高原习服能力,是预防和减轻急性高原反应的最好策略。低氧预适应是指机体经一次或多次短暂、非致死性低氧刺激后,机体获得的对后续更长时间或更严重低氧性损伤的耐受性。低氧预适应作为一种通过内源性保护机制来提高机体缺氧耐力的有效方法,是促进高原习服的重要措施。     

低氧诱导因子家族研究进展

低氧能诱导编码促红细胞生成素基因的转录,过程的具体分子机理一直不清.低氧诱导因子家族的克隆及其调控许多目的基因表达的发现,丰富了我们对机体氧感受的分子机理的认识.同时低氧诱导因子家族中各因子的表达差异,及其之间的相互调控,低氧诱导因子在低氧条件下的作用机理,对目的基因的调控及相互之间差异的阐明,对理解许多与组织缺氧有关的重要疾病如心血管疾病、中风、慢性阻塞性肺疾病,特别是肿瘤的病理生理过程有重要意义.     

低氧影响干细胞成骨分化的研究进展

氧稳态是机体或细胞正常功能所必需的, 低氧是人正常发育的一个重要的生理因素,并参与许多疾病的发生、发展.在骨发育过程中, 组织和细胞缺氧是经常存在的.体内生长板软骨增殖区氧浓度仅为 2%-5%, 肥大区氧浓度为 0.15%-1%[1].机体损伤后,由于损伤部位血流中断或血肿形成,造成局部氧分压降低.在骨折血流中断处,中央部位氧分压甚至降低到0%-2%[2,3].骨折修复需要机体在骨折部位重建血运,以便吸收损伤组织和转运营养物质.     

低氧和低氧游泳大鼠心肌糖原含量与右室功能的变化

目的：观察慢性低氧及低氧游泳大鼠心肌糖原含量的变化，探讨其与右心舒缩功能升降的关系。方法：采用低压舱模拟海拔5000 m连续低氧及低氧游泳大鼠模型，用比色法测定其心肌糖原含量；用右心导管法经RM-6000生理多导记录仪记录右心舒缩功能指标。结果：大鼠心肌糖原含量在低氧早期即显著下降，随低氧时间的延长，呈较明显进一步下降的趋势，而右心功能则逐渐增强；低氧游泳组大鼠右心功能明显增强，其心肌糖原含量接近平原对照水平，显著高于单纯低氧组。结论：大鼠在低氧条件下适量作功（游泳），可能有利于机体的低氧适应。     

基于复杂度的心率变异性分析研究进展

一、引言 心率变异性（heart rate variability,HRV）分析是一种敏感的无创伤性的评价心脏自主神经系统（autonomic nervous system,ANS）功能的定量方法。以往HRV分析多用标准差、直方图及频谱法等线性分析方法,虽可反映总体的心率变异度,但掩盖了瞬时心搏变化。1984年Ritzenberg等从狗的心电图中首次发现心脏搏动具有混沌现象,此后,许多研究者,对这方面进行了研究HRV信号被普遍认为是混沌或含有混沌成分的信号,     

CD8~+CD28~-调节性T细胞的生物学特性及其与疾病的相关性研究进展

CD8+CD28-调节性T细胞(T regulatory cells,Treg)是具有免疫调节功能的异质性细胞群,在维持机体免疫功能稳态及建立免疫耐受中发挥着重要作用,其功能缺失或数量改变与衰老、肿瘤、感染、移植排斥、自身免疫疾病等的发生发展密切相关。CD8+CD28-Treg经体外诱导而来,通过细胞间直接接触或分泌抑制性细胞因子(IFN-γ、IL-6、IL-10)发挥免疫调节功能,但目前尚未明确其独特表型。对CD8+CD28-Treg进行深入研究将有助于了解机体免疫调节机制,进而对免疫相关疾病进行有效的干预。     

缺血/低氧相关疾病微小RNA-210研究进展

 缺血/低氧是临床许多疾病的病理生理过程之一，而miRNA-210以其在缺血/低氧状态下的稳定性和功能的多样性引起了人们广泛关注。本文分析了在缺血/低氧状态下miRNA-210对线粒体新陈代谢和血管生成的影响；并且进一步阐述了miRNA-210在心肌梗死，中风和肿瘤等缺血/低氧性损伤疾病中的作用。     

Effect of hypobaric hypoxia on heart rate variability during exercise: a pilot field study

The influence of hypoxia on heart rate variability (HRV) has been studied under resting conditions with mixed results. Differences have been found in physiological responses to normobaric versus hypobaric hypoxia. Our aim was to study the influence of hypobaric hypoxia on HRV during physical exercise to determine whether HRV changes due to the exercise-induced heart rate (HR) increase or whether hypoxia itself exerts an influence. We tested nine healthy non-acclimatised white males (age = 43 ± 7 years) at 400 and 4,200 m during exercises. At 400 m HRV was measured at 50% and 75% maximal oxygen uptake (VO₂ max). At 4,200 m HR was kept equal as during exercise at 400 m by adjusting the intensity of step testing. The Poincaré plot as a non-linear method of HRV analysis was used, where the shape of the ellipse depending on HRV is expressed by two parameters, SD1 and SD2 (correlating to parasympathetic activity and both sympathetic and parasympathetic activity, respectively). We established a decrease in SD2 and an insignificant decrease in SD1 at medium HR at 4,200 m compared to 400 m. Both parameters showed similar tendencies during high-intensity exercise. Our results indicate that hypobaric hypoxia itself exerts an influence on HRV at a moderate HR.     

Automated detection of perinatal hypoxia using time–frequency-based heart rate variability features

Perinatal hypoxia is a cause of cerebral injury in foetuses and neonates. Detection of foetal hypoxia during labour based on the pattern recognition of heart rate signals suffers from high observer variability and low specificity. We describe a new automated hypoxia detection method using time–frequency analysis of heart rate variability (HRV) signals. This approach uses features extracted from the instantaneous frequency and instantaneous amplitude of HRV signal components as well as features based on matrix decomposition of the signals’ time–frequency distributions using singular value decomposition and non-negative matrix factorization. The classification between hypoxia and non-hypoxia data is performed using a support vector machine classifier. The proposed method is tested on a dataset obtained from a newborn piglet model with a controlled hypoxic insult. The chosen HRV features show strong performance compared to conventional spectral features and other existing methods of hypoxia detection with a sensitivity 93.3 %, specificity 98.3 % and accuracy 95.8 %. The high predictive value of this approach to detecting hypoxia is a substantial step towards developing a more accurate and reliable hypoxia detection method for use in human foetal monitoring.     

Body position and cardiac dynamic and chronotropic responses to steady-state isocapnic hypoxaemia in humans

Neural mediation of the human cardiac response to isocapnic (IC) steady-state hypoxaemia was investigated using coarse-graining spectral analysis of heart rate variability (HRV). Six young adults were exposed in random order to a hypoxia or control protocol, in supine and sitting postures, while end-tidal PCO2 (PET,CO2) was clamped at resting eucapnic levels. An initial 11 min period of euoxia (PET,O2 100 mmHg; 13.3 kPa) was followed by a 22 min exposure to hypoxia (PET,O2 55 mmHg; 7.3 kPa), or continued euoxia (control). Harmonic and fractal powers of HRV were determined for the terminal 400 heart beats in each time period. Ventilation was stimulated (P < 0.05) and cardiac dynamics altered only by exposure to hypoxia. The cardiac interpulse interval was shortened (P < 0.001) similarly during hypoxia in both body positions. Vagally mediated high-frequency harmonic power (Ph) of HRV was decreased by hypoxia only in the supine position, while the fractal dimension, also linked to cardiac vagal control, was decreased in the sitting position (P < 0.05). However, low-frequency harmonic power (Pl) and the HRV indicator of sympathetic activity (Pl/Ph) were not altered by hypoxia in either position. These results suggest that, in humans, tachycardia induced by moderate IC hypoxaemia (arterial O2 saturation Sa,O2 85 %) was mediated by vagal withdrawal, irrespective of body position and resting autonomic balance, while associated changes in HRV were positionally dependent.     

Autonomic cardiovascular response to acute hypoxia and passive head-up tilting in humans

Acute hypoxia may alter autonomic cardiovascular reflexes during orthostasis. Heart rate variability (HRV), arterial blood pressure (MAP), and respiratory sinus arrhythmia (RSA) were recorded during supine (SUP) and passive head up tilt (HUT) in eight healthy humans, spontaneously breathing either room air or 10 % O₂ in N₂. In the time domain, heart rate increased and variability decreased with HUT in both trials, with no difference between trials. In the frequency domain, normalized low frequency HRV increased, and normalized high frequency HRV decreased with HUT in both trials, with no difference between trials. MAP was 74.9 (8.6) and 77.5 (11.7) mmHg when SUP in the room air and hypoxia trials, respectively. A significant increase in MAP occurred with HUT in the room air trial but not in the hypoxia trial. In both trials, end tidal CO₂ decreased with HUT, with no difference between trials. In the room air trial, end tidal O₂ increased with HUT, whereas during the hypoxia trial, end tidal O₂ decreased with HUT. The distribution of heart beats relative to the phase of ventilation (%HB_IN and %HB_OUT) was similar in both trials: the %HB_IN was 43.5 (3.3) % and %HB_OUT was 56.5 (4.2) % breathing room air when SUP, and 45.5 (3.0) and 54.5 (3.2) when hypoxic and SUP. For both trials, this distribution did not change with HUT. As both HRV and RSA showed similar responses to HUT when spontaneously breathing either room air or 10 % O₂ in N₂, we suggest that autonomic cardiovascular reflexes are preserved during acute hypoxia.     

Blunted cardiac autonomic responsiveness to hypoxemic stress in healthy older adults.

Supine resting cardiac dynamics and responses to steady-state hypoxemia were investigated in six healthy older (59-72 yrs) adults using coarse-graining spectral analysis of heart rate variability (HRV) and were compared to six young (22-29 yrs) adults studied previously (Lucy et al., 2000). End-tidal carbon dioxide pressure (PETCO2) was clamped at 1-2 mmHg above the usual resting value for 11 min of euoxia (PETO2 100 mmHg), followed by 22 min of hypoxia (PETO2 55 mmHg). During euoxia, vagally mediated harmonic and fractal power of HRV of older adults was minimal. Hypoxia induced an increase in ventilation, p < 0.01, and heart rate, p < 0.05. The heart rate increase (mean +/- SE) of 0.23 +/- 0.08 beats.min-1 per 1% decrease in arterial O2 saturation was 25% of that demonstrated previously by young subjects, p < 0.001. In older adults, HRV spectral power remained unchanged during hypoxia, providing further evidence of an age-related blunting of cardiac autonomic function.     

The effect of sucrose ingestion on autonomic nervous system function in young subjects during acute moderate hypoxia

Cardiac arrhythmias are associated with an increase in sympathetic activity (reflected in increased heart rate) and a simultaneous decrease in rhythmical fluctuations of sympathetic activity [reflected in decreased heart rate variability (HRV)]. As hypoxia is a well known trigger for cardiac arrhythmias, and carbohydrate loading a known sympatho-excitatory stimulus, the present study investigated if carbohydrate loading affects the cardiac response to acute hypoxic challenge. Fourteen subjects ingested a sucrose solution or an equal volume of water and spectral analysis of HRV was used to determine HRV components in normoxia and acute, normobaric hypoxia. Compared to the control condition, ingestion of carbohydrates increased heart rate, spectral power of nLF (P < 0.02) and LF/HF ratio (P < 0.003), and decreased spectral power of nHF (P < 0.03) during hypoxia. Carbohydrate ingestion thus intensified cardiac autonomic modulation during acute hypoxia and may therefore act as a beneficial protective mechanism against the disturbances of cardiac rhythm in hypoxic conditions. Dr. Jerica Maver deceased.     

温度对心率和心率变异的影响

心率变异（heart rate variability,HRV）是判断自主神经活动最好的定量指标,有时域、频域和非线性等研究方法.频域方法适用于短时程记录,而时域法对分析长时程记录较为理想.HRV的发生基础是自主神经对心率的调节作用,反映了神经体液因素与窦房结相互作用的平衡关系.心率变异受诸多外周和中枢因素的影响,体温及环境温度的变化影响着心血管活动的调节,是HRV的重要起因.极低频（very low frequencies,VLF）功率受温度刺激（如低体温和体温调节活动）的调制,皮肤降温不会特异的影响此频带,表明功率谱中特别频带的改变依赖于体温调节激发模式,而不是体温调节本身.中枢神经系统的损伤可引起心脏自主神经的异常活动并降低HRV,低体温处理可以使HRV的降低更显著.因此研究体温及环境温度与HRV的关系具有非常重要的实用价值.     

Reserved higher vagal tone under acute hypoxia in Tibetan adolescents with long-term migration to sea level

Tibetans are known as one of the largest and oldest high-altitude natives in the world and are among the best high-altitude-adapted ethnic groups. They exhibit greater vagal tone and less sympathetic stimulation than acclimatized lowlanders at high altitudes. Whether young native Tibetans who had spent long-term residence (more than 3 years) at sea level still reserved their unique autonomic characteristics was the main aim of this study. Heart rate variability (HRV) of 10 native young Tibetan male students and 12 Han counterparts were measured at resting supine position at sea level and 1 h after ascent to 3,700 m in a hypobaric chamber (PO(2) = 13.4 kPa). At sea level, Tibetans showed lower heart rate (HR) and greater HRV. At 3,700 m, the increase of HR was greater in the Hans than in the Tibetans, and the HRV was significantly diminished in the Han group but not in the Tibetan group. The results suggested that Tibetans had a greater parasympathetic dominance over the heart at rest, and acute moderate (3,700 m) hypoxia did not influence their HRV significantly, but it did on the Han subjects. We concluded that the long-term residence of the Tibetans at sea level did not change their unique characteristics of the autonomic systems.     

Resting sympathetic arousal moderates the association between parasympathetic reactivity and working memory performance in adults reporting high levels of life stress

The neurovisceral integration model stipulates that autonomic function plays a critical role in the regulation of higher‐order cognitive processes, yet most work to date has examined parasympathetic function in isolation from sympathetic function. Furthermore, the majority of work has been conducted on normative samples, which typically demonstrate parasympathetic withdrawal to increase arousal needed to complete cognitive tasks. Little is known about how autonomic regulation supports cognitive function in populations exposed to high levels of stress, which is critical given that chronic stress exposure alters autonomic function. To address this, we sought to characterize how parasympathetic (high‐frequency heart rate variability, HF‐HRV) and sympathetic (preejection period, PEP) measures of cardiac function contribute to individual differences in working memory (WM) capacity in a sample of high‐risk women. HF‐HRV and PEP were measured at rest and during a visual change detection measure of WM. Multilevel modeling was used to examine within‐person fluctuations in WM performance throughout the task concurrently with HF‐HRV and PEP, as well as between‐person differences as a function of resting HF‐HRV and PEP levels. Results indicate that resting PEP moderated the association between HF‐HRV reactivity and WM capacity. Increases in WM capacity across the task were associated with increases in parasympathetic activity, but only among individuals with longer resting PEP (lower sympathetic arousal). Follow‐up analyses showed that shorter resting PEP was associated with greater cumulative risk exposure. These results support the autonomic space framework, in that the relationship between behavior and parasympathetic function appears dependent on resting sympathetic activation.     

Does preprocessing change nonlinear measures of heart rate variability?

This work investigated if methods used to produce a uniformly sampled heart rate variability (HRV) time series significantly change the deterministic signature underlying the dynamics of such signals and some nonlinear measures of HRV. Two methods of preprocessing were used: the convolution of inverse interval function values with a rectangular window and the cubic polynomial interpolation. The HRV time series were obtained from 33 Wistar rats submitted to autonomic blockade protocols and from 17 healthy adults. The analysis of determinism was carried out by the method of surrogate data sets and nonlinear autoregressive moving average modelling and prediction. The scaling exponents , ₁ and ₂ derived from the detrended fluctuation analysis were calculated from raw HRV time series and respective preprocessed signals. It was shown that the technique of cubic interpolation of HRV time series did not significantly change any nonlinear characteristic studied in this work, while the method of convolution only affected the ₁ index. The results suggested that preprocessed time series may be used to study HRV in the field of nonlinear dynamics.