模拟急进高原环境对糖尿病大鼠心肌损伤的影响

目的 探讨模拟急进高原环境对糖尿病大鼠心肌损伤的影响及机制。方法 采用雄性Wistar大鼠建立2型糖尿病大鼠模型,依据模拟急进不同海拔高原环境,采用随机数字表法将50只大鼠分为5组：空白对照组（C组）、3 700 m正常组（C37组）、5 000 m正常组（C50组）、3 700 m糖尿病组（D37组）、5 000 m糖尿病组（D50组）。对大鼠进行心电图检查、动脉血气分析及血清心肌酶谱检测;并取心肌病理标本进行HE、PAS、TUNEL染色,观察形态学变化及细胞凋亡情况;利用lncRNA芯片技术检测大鼠心肌组织lncRNA表达谱的差异,筛选出差异表达的lncRNA。结果 D37组大鼠心电图可见频发室性早搏,D50组大鼠可见ST段压低、T波改变;血气分析显示,与C组、C37组和C50组比较,D37组和D50组大鼠的pH值和PaO2均显著下降（P<0.05）,肌酸激酶同工酶MB（CK-MB）水平升高（P<0.05）;D37组和D50组心肌形态学检查可见心肌细胞肥大、糖原物质大量沉积,细胞凋亡比例增高,D50组伴有炎性细胞浸润;心肌lncRNA芯片分析发现,D37组与C37组、D50组与C50组差异表达lncRNA的功能主要集中在调控α1-肾上腺素受体、肌动蛋白活性和压力诱导的心肌肥大。mRNA差异基因KEGG富集分析显示,参与肥厚性心肌病、扩张性心肌病、心肌收缩等信号通路的Myh6、Myh7、Actc1等基因参与了心肌损伤的过程。结论 糖尿病大鼠在急进高原状态时心肌细胞凋亡增加,同时激活了诱导心肌细胞肥大的相关基因,较正常大鼠更容易出现心肌损伤。     

急进高原人群脑血流量测定对急性高原病易感人群预测的临床与实验观察

本文对三组急进高原人群资料回顾分析了急进高海拔区（〉４５００Ｍ）人群脑血流量测定的临床意义。结果表明急进高原人群脑血流量较在低海拔区明显增高，有显著性差异；而急进高压人群中的急性高原反应和急性高原病患者脑血流量又显著高原适应人群。采用药物和吸氧治疗高原人群中急性高原反应人群，脑血流量明显降低，急进高原人群高原反应程度和急性高原病的发病率亦相应降低。因此监测急进高原人群的脑血流量，不仅可以早期发现急     

颈淋巴引流阻滞对清醒自由活动大鼠的血压的影响

目的：观察颈淋巴引流阻滞（CLB）对清醒自由活动大鼠的血压的影响,并初步探讨其机制。方法：采用SD大鼠,随机分为假手术组（Sham组）和CLB组。应用监测清醒自由活动大鼠血流动力学变化的手段,分别连续记录两组大鼠在假手术和CLB手术术前及术后第1、3、7、11、15d收缩压（SBP）、舒张压（DBP）、心率（HR）的变化。测定两组大鼠术前、术后第1、7及15d压力感受性反射敏感性（BRS）。脱机分析其相应的血压波动性（BPV）、心率变异性（HRV）。结果：CLB术后第1天SBP、DBP、MAP、HR及BRS下降,第7天降至最低,BRS在7d后无明显恢复,而血压及心率随着CLB时间的延长呈先下降后上升。相反,HRV、BPV先上升后下降。结论：CLB可导致清醒自由活动大鼠血压降低,心血管系统神经调节功能下降。     

药物对高原移居者睡眠呼吸紊乱警觉性作用初步研究

目的应用心理生理测验的途径检测探索高海拔地区抗低氧药物对移居者睡眠呼吸紊乱(SDB)警觉性的作用.方法选择驻守在海拔5380米高原12个月青年士兵24人,随机分为甲、乙两组,采用DDX-200型电脑多功能心理生理能力测试仪和ASC-545型血氧仪,监测前晚11.30时和早晨8.20时静息状态下的脑功能和血氧饱和度(SaO2),衡量其警觉性.甲组口服三普红景天胶囊,乙组口服乙酰唑胺片;均一次服药25天后,重复监测前晚和早晨静息状态下的脑功能及SaO2,并进行服药前后的对比评定.结果甲乙两组服药前晚、晨SaO2比较相近似,无显著性差异(p＞0.05)、服药后甲组晚、晨SaO2显著高于服药前(p＜0.05);服药后乙组晨SaO2显著高于服药前(p＜O.01).甲、乙组服药前晚、晨比较,视觉注意分配无显著性差异(p＞0.05);缺失记忆测验、甲组晚晨与乙组比较错误次数显著增多(p＜O.01),服药后亦相同.服药后甲组视觉注意分配测验晚操作总次数、正确次数,晨正确次数显著高于服药前(p＜0.01或p＜0.05),操作平均时间显著低于服药前(p＜O.01);缺失记忆测验晚错误次数显著多于服药后(p＜0.01);服药后乙组晚视觉注意分析总次数、正确次数显著多于服药前(p＜0.01或p＜0.05),服药前晚操作平均时间、晨错误次数、操作平均时间显著多于服药后(p＜0.01或p＜0.05);服药前缺失记忆测验晚晨错误次数显著我于服药后(p＜0.05).甲乙组视觉注意分配测验,甲组服药后晚测验总次数、正确次数显著多于乙组(p＜0.01),晨测验次数、正确次数、错误次数显著多于乙组(p＜0.01或p＜0.05).结论红景天与乙酰唑胺均能不同程度的改善和调节高原睡眠呼吸质量,减轻和改善SDB,提高大脑的警觉性水平.     

戊巴比妥钠麻醉持续时间对犬的血压、体温、呼吸和心电的影响

目的：观察在戊巴比妥钠麻醉剂量下,犬的血压、体温、呼吸频率和心电图（标准Ⅱ导联）随麻醉持续时间的变化情况。方法：10只犬用戊巴比妥钠按30mg·kg^-1静脉注射全身麻醉,颈动脉插管测血压,电子温度计量肛温,呼吸波传感器系于胸部测呼吸频率,四肢接标准Ⅱ导联检测心电图,连续观察6小时（以初始剂量的1／5-1／4维持麻醉）。结果：随麻醉时间的延长,犬的体温明显下降、呼吸频率先抑制后回升,心率减慢、QT间期延长,血压变化不明显。结论：该麻醉方法对犬的体温和心电有明显影响,在麻醉初期对呼吸也有影响,对血压的影响不明显。     

电磁辐射对清醒大鼠动脉收缩压的影响及其机制研究

目的:观察电磁辐射(EMR)对大鼠整体血压的影响并初步探讨其机理。方法:用无创性的尾套式大鼠动脉血压测量仪观察一定场强和脉冲次数的EMR照后不同时间内清醒大鼠动脉收缩压的变化规律,并观察血液中前列环素(PGI2)、血栓烷素(TXA2)、内皮素(ET),心钠素(ANP)、一氧化氮浓度及一氧化氮合酶活性的变化。结果:照射后的大鼠的动脉血压先升高,维持至第2 h,开始下降,在第12 h下降至最低点,而后开始缓慢回升,在到第24 h,逐渐恢复接近正常水平。在收缩压变动的最显著的第12 h,血浆前列腺环素和心钠素的浓度明显降低,内皮素含量升高,血栓素在照射后没有显著改变,NOS活性升高,NO含量略有升高,但无显著差异。结论:EMR照射后,大鼠血压呈规律性改变,内皮素、心钠素、前列环素参与了辐射引起的血压波动,NO/NOS系统在其中的作用尚不能肯定。     

急进高原人群脑血流量测定对急性高原病易感人群预测的临床与实验观察

本文对三级急进高原人群资料回顾分析了急进高海拔区（＞4500M）人群脑皿流量测定的临床意义。结果表明急进高原人群脑血流量较在低海拔区明显增高，有显著性差异；而急进高原人群中的急性高原反应和急性高原病患者脑血流量又显著高于高原适应人群。采用药物和吸氧治疗急进高原人群中急性高原反应人群，脑血流量明显降低，急进高原人群的高原反应程度和急性高原病的发病率亦相应降低。因此监测急进高原人群的脑血流量，不仅可以早期发现急性高原反应及急性高原病患者，更可以预测急性高原易感者，可为急性高原病的早期治疗和预防，扩大高原适应人群提供重要的理论依据。     

高原低氧对大鼠下丘脑谷氨酸、天门冬氨酸和NOS的影响

目的:观察高原低氧大鼠下丘脑谷氨酸(Glu)、天门冬氨酸(Asp)和一氧化氮合酶(NOS)的变化。方法:应用氨基酸测定和NADPH-d组化法,检测高原低氧模型大鼠下丘脑Glu、Asp含量和NADPH-d阳性神经元的数量。结果:高原低氧大鼠下丘脑Glu、Asp含量明显增多,室旁核、视上核可见密集深染的NADPH-d阳性神经元;用NMDA受体拮抗剂氯氨酮(Ketamine)和AP-V对高原低氧大鼠进行预处理后置于低压氧舱,观察到大鼠下丘脑室旁核、视上核NADPH-d阳性神经元数明显少于相应时间的高原低氧组(P＜0.01)。结论:NMDA受体可能参与了高原低氧引起的下丘脑NOS的表达。     

阻塞性睡眠呼吸暂停低氧对脑缺血大鼠海马区神经细胞自噬的影响

目的:探讨阻塞性睡眠呼吸暂停(obstructive sleep apnea hypoxia hypoxia,OSAH)低氧对脑缺血大鼠海马区神经细胞自噬的影响。方法:雄性Wistar大鼠采用数字随机法随机分成假手术组(SO组)、单纯脑缺血再灌注组(I/R组)、OSAH低氧7 d脑缺血再灌注组(IH7+I/R组)、OSAH低氧21 d脑缺血再灌注组(IH21+I/R组)。造模前,IH7+I/R组、IH21+I/R组分别给予间歇性低氧7、21 d。采用改良的Pulsinelli四血管阻断法制备脑缺血再灌注模型,术后24 h,H-E染色观察海马区神经细胞形态变化,RT-PCR、免疫组织化学检测大鼠脑组织海马区mTOR、beclin--1表达情况。结果:与假手术组比较,I/R组大鼠在各时间点均神经元结构损伤;免疫组织化学显示mTOR、beclin--1蛋白免疫阳性细胞数增加;RT-PCR示mTOR、beclin-mRNA表达增强。与I/R组比较,OSAH低氧各组大鼠在各时间点,H-E染色示神经元结构损伤加重;免疫组织化学示mTOR、beclin--1蛋白免疫阳性细胞数增加;RTPCR示mTOR、beclin-1 mRNA表达增强;上述变化在IH21+I/R组更为显著。结论:OSAH低氧加重脑缺血后海马神经元的自噬性损伤。     

小波变换用于从血压信号中提取呼吸及心率信息的研究

本文提供了一种新的数字信号处理工具一小波变换和小波分析程序流程图,可用于重量及其它学科科研实验研究。文中给出了利用Gauss一介导数小波变换从家兔动脉血压信号中提取呼吸频率及心率的方法。     

Acute mountain sickness relates to sea-level partial pressure of oxygen

The aim of this study was to clarify the relationships between acute mountain sickness (AMS), studied during an expedition in the Andes, and some physiological parameters determined before the expedition, i.e. biometrical characteristics of the subjects [maximal oxygen consumption ( ) body fat content, body mass index], functional pulmonary tests (forced vital capacity, forced expiratory volume at the first second), ventilatory or cardiac responses measured at 4 500 m [hypoxic ventilatory responses (HVR) 4 500 and hypoxic cardiac responses (HCR) 4 500, respectively), cold pressor responses. To achieve this objective, 11 subjects were firstly submitted to a hypobaric poïkilocapnic hypoxic test (589 hPa, 4 500 m) at rest and during exercise to study minute volume, respiratory frequency, end tidal partial pressure of O₂ (P _ETO₂) and CO₂, HVR 4 500, HCR 4 500 and to a cold pressor test of the hand (5 min in 5°C cold water) to study heart rate, blood pressure and skin temperature changes. The AMS was assessed daily by questionnaire during a 12-day expedition in the Andes following both Hackett's method and Environmental Symptoms Questionnaire (modified ESQ 11). Maximal AMS-Hackett score, maximal AMS-ESQ score and mean AMS-ESQ score were defined. The quantifications of AMS following the two methods were correlated. No significant relationships were observed between mean AMS-ESQ score and the biometrical characteristics of the subjects, the functional pulmonary tests, HVR 4 500, HCR 4 500 or the cold pressor responses. However, it appeared that the mean AMS-ESQ score was correlated withP _ETO₂ measured at rest and during exercise (50% ) both in hypoxia and normoxia. A closer linear relationship was observed during the exercise in normoxia (r = – 0.92,P < 0.0001). These results could suggest that AMS was related to a relative alveolar hypoventilation more in relation to breathing pattern than HVR.     

Normo or hypobaric hypoxic tests: propositions for the determination of the individual susceptibility to altitude illnesses

Assessment of individual susceptibility to altitude illnesses and more particularly to acute mountain sickness (AMS) by means of tests performed in normobaric hypoxia (NH) or in hypobaric hypoxia (HH) is still debated. Eighteen subjects were submitted to HH and NH tests (PIO₂=120 hPa, 30 min) before an expedition. Maximal and mean acute mountain sickness scores (AMSmax and mean) were determined using the self-report Lake Louise questionnaire scored daily. Cardio-ventilatory (f, V_T, PetO₂ and PetCO₂, HR and finger pulse oxymetry SpO₂) were measured at times 5 and 30 min of the tests. Arterial (PaO₂, PaCO₂, pH, SaO₂) and capillary haemoglobin (Hb) measurements were performed at times 30 min. Hypoxic ventilatory (HVR) and cardiac (HCR) responses, peripheral O₂ blood content (CpO₂) were calculated. A significant time effect is found for ΔSpO₂ (P = 0.04). Lower PaCO₂ (P = 0.005), SaO₂ (P = 0.07) and higher pH (P = 0.02) are observed in HH compared to NH. AMSmax varied from 3 to12 and AMSmean between 0.6 and 3.5. In NH at 30 min, AMSmax is related to PetO₂ (R = 0.61, P = 0.03), CpO₂ (R = −0.53, P = 0.02) and in HH to CpO₂ (R = −0.57, P = 0.01). In NH, AMSmean is related to Δf (R = 0.46, P = 0.05), HCR (R = 0.49, P = 0.04), CpO₂ (R = −0.51, P = 0.03) and, in HH at 30 min, to V_T (R = 0.69, P = 0.01) and a tendency for CpO₂ (R = −0.43, P = 0.07). We conclude that HH and NH tests are physiologically different and they must last 30 min. CpO₂ is an important variable to predict AMS. For practical considerations, NH test is proposed to quantify AMS individual susceptibility using the formulas: AMSmax = 9.47 + 0.104PetO₂(hPa)–0.68CpO₂ (%), (R = 0.77, P = 0.001); and AMSmean = 3.91 + 0.059Δf + 0.438HCR–0.135CpO₂ (R = 0.71, P = 0.017).     

Distortion product otoacoustic emissions for assessment of intracranial hypertension at extreme altitude?

The levels of distortion product otoacoustic emissions (DPOAEs) change at frequencies between 0.75 and 1.5 kHz along with intracranial pressure (ICP) and DPOAEs are suggested for monitoring ICP changes. Elevated ICP plays a major role in high-altitude disease, but direct measurement is unlikely to be feasible at high altitudes. The aim of the presented study was to measure DPOAEs at extreme altitudes in order to determine whether information about elevated ICP can be obtained. Data are presented from DPOAE measurements at the frequencies 1, 1.5, 2, 3 and 4 kHz in 13 climbers during an ascent to Gasherbrum II (8,035 m) up to an altitude of 7,400 m. Valid DPOAE measurements could be obtained in all climbers. DPOAE levels exhibited great variability concerning both the affected frequency range and the change. As expected due to elevated ICP, DPOAE levels decreased in some of the climbers at 1 kHz. However, an even more pronounced decline of DPOAE levels was observed at 3 and 4 kHz, which cannot be explained by intracranial hypertension. Possible other reasons for DPOAE level changes at extreme altitude are hypoxia, increased serum osmolarity and unbalanced middle ear pressure. Only one climber developed severe acute mountain sickness with clinical signs of intracranial hypertension. The most pronounced decline of DPOAEs at 1 kHz was seen on that occasion, which suggests a possible use of DPOAEs for detection of intracranial hypertension and early detection of high-altitude cerebral edema.     

Effects of high-altitude exposure on vascular endothelial growth factor levels in man

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen and permeability factor that is inducible by hypoxia. Its contribution to high-altitude illness in man is unknown. We measured VEGF levels in 14 mountaineers at low altitude (490 m) and 24 h after their arrival at high altitude (4,559 m). At high altitude, VEGF increased from [mean (SEM)] 32.5 (9.2) to 60.9 (18.5) pg·ml^–1 (P<0.004) in the arterial blood, and from 15.9 (2.9) to 49.3 (15.9) pg·ml^–1 (P=0.0001) in the mixed venous blood. Whereas at low altitude venous and arterial VEGF levels were not statistically different from each other (P=0.065), the VEGF concentration was significantly lower in venous than in arterial blood samples at high altitude (P=0.004). The pulmonary capillary VEGF concentration remained unchanged at high altitude [14.8 (2.5) vs 17.1 (5.4) pg·ml^–1, P=0.85]. VEGF levels in the nine mountaineers who developed symptoms of acute mountain sickness (AMS), and in the six subjects who had radiographic evidence of high-altitude pulmonary edema were similar to those in subjects without symptoms. VEGF was not correlated with either AMS scores, mean pulmonary arterial pressures, arterial partial pressure of O₂, or alveolar-arterial O₂ gradients. We conclude that VEGF release is stimulated at high altitude, but that VEGF is probably not related to high-altitude illness. Electronic Publication     

Normoxic induction of cerebral HIF-1α by acetazolamide in rats: Role of acidosis

Acetazolamide has been recognized as an effective treatment for acute mountain sickness. The efficacy of acetazolamide is related to metabolic acidosis, which promotes chemoreceptors to respond to hypoxic stimuli at altitude. In this study, adult male Sprague–Dawley rats were treated with acetazolamide (100 mg/kg or 50 mg/kg, I.P.) for 3 days. Primary cultured cortical neurons and PC12 cell lines were exposed to acidosis-permissive (pH 6.5) or standard (pH 7.2) media for 20 h. HIF-1α and its target genes were assayed by Western blot, real-time PCR, HIF-1 DNA-binding assay and chloramphenicol acetyltransferase reporter gene assay. HIF-1α protein level and HIF-1 DNA-binding activities were increased in cerebral cortices of rats treated with acetazolamide. Moreover, the mRNA levels of erythropoietin, vascular endothelial growth factor, and glucose transporter-1 also increased. The HIF-1α protein level and activity of HIF-driven chloramphenicol acetyltransferase reporters of cortical neurons and PC12 cells treated with acidosis media were significantly enhanced. We conclude that the normoxic induction of HIF-1α and HIF-1 mediated genes by acetazolamide may mediate the effect of acetazolamide in the reduction of symptoms of acute mountain sickness.     

Functional involvement of central nervous system at high altitude

Acute mountain sickness is a common discomfort experienced by unacclimatized persons on ascent to high altitude. We tested the hypothesis that exposure to high altitude affects cortical excitability using transcranial magnetic stimulation. We specifically analyzed the motor cortex excitability in normal subjects at high altitude and in a control condition near sea level. Mean resting motor threshold (RMT) was significantly higher at high altitude than at sea level (69.3 ± 10.4 versus 56.3 ± 10.9%; P = 0.042). Mean short intracortical inhibition (SICI) was significantly lower at high altitude than at sea level (percentage of test motor-evoked potential = 79.3 ± 19.8 versus 28.7 ± 17.5%; P = 0.0004). Symptoms of acute mountain sickness correlated with resting motor threshold changes induced by high altitude (R ² = 0.53, P = 0.037). SaO₂ correlated with SICI changes induced by high altitude (R ² = 0.45, P = 0.036). We suggest that high altitude deeply changes cortical excitability by affecting both inhibitory and excitatory circuits and that this is reflected in acute mountain sickness symptoms. G. Miscio sadly died in autumn 2007.     

Increased hypoxic ventilatory response during hypovolemic stress imposed through head-up-tilt and lower-body negative pressure

The aim of this study was to quantify the influence of head-up-tilt (HUT) on the isocapnic hypoxic ventilatory response (HVR) in man, and to investigate the effect of orthostatic blood shifts separately from other gravitational effects by the application of lower-body negative pressure (LBNP) with subjects in a horizontal position. HVR was measured in 15 subjects during passive HUT from 0° to 85° as well as during −7° head-down-tilt and while they were in a sitting position. In a subgroup of eight subjects the effect of 85° HUT was compared to a corresponding LBNP of −70 mbar on HVR. Moreover, by imposing graded HUT (7°, 15°, 30°, 50°) and LBNP (−15, −30 mbar) we studied the effect of low-level orthostatic stress on HVR. Ventilation, end-tidal partial pressure of CO₂, heart rate and blood pressure were recorded continuously for 1 min before, and during HVR. HVR was significantly increased by ≅50% through both 85° HUT and −70 mbar LBNP as compared to 0° and 0 mbar, respectively, at unchanged mean arterial pressure. Low-level HUT and LBNP had no effect on HVR. It was concluded that the orthostatic HVR increase may be attributable to caudal blood shifts (i.e., central hypovolemia). This HVR increase requires a pronounced hypovolemic stress but no decrease in arterial blood pressure. It is suggested that a central interaction of arterial and cardiopulmonary baroreceptors is underlying this response. Their separate contribution remains to be assessed. Accepted: 14 October 1999     

光纤传感器检测呼吸压

本文介绍一种光纤呼吸传感器，用于呼吸压检测，其灵敏度比扩散硅式半导体压力传感器高，低频性能比压电式传感器好，实测结果满意     

Systemic hypoxia affects cardiac autonomic activity and vascular hemodynamic control modulated by physical stimulation

This study investigates how various hypoxic interventions affect cardiac autonomic activity and hemodynamic control during posture change and the Valsalva maneuver. Ten healthy sedentary men exposed to 12, 15 and 21% O₂ for 1 h in a normobaric hypoxia chamber in a random order. Before and after various O₂ concentrations were administered, subjects performed the sit-up test and Valsalva maneuver, respectively. An impedance plethysmography was utilized to measure blood pressure (BP) and vascular hemodynamics, whereas spectral analysis of heart rate variability (HRV) was performed to determine cardiac autonomic activity. Analytical results can be summarized as follows: while the patient rests in a supine position, exposure to 12% O₂ reduces the ratio of lower to upper extremity systolic BP, which is accompanied by (1) suppressed arterial reactive hyperemia and increased venous flow resistance, as well as (2) decreased total power and high frequency (HF) and increased low frequency (LF) and the ratio of LF to HF. Moreover, the hypoxia-induced changes of time and frequency domains in HRV at resting supine disappear following the sit-up test, whereas this hypoxic exposure attenuates the BP and heart rate responses to the Valsalva maneuver. Conversely, resting and physical stimuli-mediated HRV and vascular hemodynamic values are unaltered by both 15 and 21% O₂ exposures. We conclude that acute hypoxic exposure affects cardiovascular autonomic functions, with reactions determined by the intervening O₂ concentrations. Moreover, the BP and cardiac autonomic responses to 12% O₂, but not 15% O₂, exposure are depressed while performing posture change and the Valsalva maneuver.     

内源性一氧化氮在急性高原病中的研究进展

1一氧化氮(nitric oxide,NO)与内源性一氧化氮(endogenous NO,eNO)NO是具有调节血管张力、血流等众多生物学作用的脂溶性气体信号分子,eNO是由L-精氨酸(L-arginine,L-Arg)经过体内一氧化氮合酶[nitric oxide synthase,NOS;主要有神经源型(neuronal NOS,nNOS)、诱导型(inducible NOS,iNOS)和内皮源型(endothelial NOS,eNOS)3种]催化合成的,广泛存在于全身组织[1].NO通过一些生物分子和细胞间相互作用参与机体的保护、调节及逆转等生理过程[2].近年来的研究发现NO在调节血管张力、抑制炎症以及抗动脉粥样硬化中发挥关键作用[1-2].