超声心动图Tei指数对不同血糖控制水平妊娠期糖尿病孕妇胎儿心功能及出生后整体心功能的评估价值

目的:探讨超声心动图Tei指数对不同血糖控制水平妊娠期糖尿病(GDM)孕妇胎儿心功能及出生后整体心功能的评估价值。方法:选择2017年2月至2019年10月期间我院产科接诊的134例GDM患者,根据血糖控制水平将其分为良好组(餐前空腹血糖≤5.3 mmol/L,餐后2 h血糖≤6.7 mmol/L,睡前血糖>3.3 mmol/L,妊娠期糖化血红蛋白<5.5%,65例)和不良组(餐前空腹血糖>5.3 mmol/L,餐后2 h血糖>6.7 mmol/L,睡前血糖≤3.3 mmol/L,妊娠期糖化血红蛋白≥5.5%,69例),另选择50例正常妊娠孕妇为对照组。分别于妊娠3238周、新生儿出生后17 d采用超声心动图测量胎儿、新生儿心功能和Tei指数。比较胎儿、新生儿心功能、Tei指数的差异。结果:不良组胎儿左室射血分数(LVEF)、二尖瓣E/A峰的速度比值(E/AMV)、右室舒张末期内径(RVDd)、右室收缩末期内径(RVDs)、左室短轴缩短率(LVFS)、左心室Tei指数、右心室Tei指数均高于良好组和对照组(P<0.05),三尖瓣E/A峰速度比值(E/ATV)低于良好组和对照组(P<0.05)。良好组LVFS高于对照组(P<0.05),良好组LVEF、E/AMV、E/ATV、RVDd、RVDs、左心室Tei指数、右心室Tei指数与对照组比较无统计学差异(P>0.05)。不良组新生儿LVEF、E/AMV、RVDd、RVDs、LVFS、左心室Tei指数、右心室Tei指数均高于良好组和对照组(P<0.05),E/ATV低于良好组和对照组(P<0.05)。良好组LVFS高于对照组(P<0.05),良好组LVEF、E/AMV、E/ATV、RVDd、RVDs、左心室Tei指数、右心室Tei指数与对照组比较无统计学差异(P>0.05)。结论:超声心动图Tei指数可敏感地反映GDM孕妇胎儿以及新生儿心功能损伤,妊娠期有效控制血糖水平有助于保护胎儿心功能。     

心脏彩超评估高血压左心室肥厚伴左心衰竭患者心功能的临床价值及与NYHA分级的关系研究

目的:探讨心脏彩超评估高血压左心室肥厚(LVH)伴左心衰竭患者心功能的临床价值,分析其超声指标与美国纽约心脏病协会(NYHA)分级的相关性。方法:选择2017年5月至2018年5月我院收治的127例高血压LVH伴左心衰竭患者为观察组,根据NYHA分级将其分为NYHAⅡ级组(41例)、Ⅲ级组(47例)、Ⅳ级组(39例),另选择100例体检的健康志愿者为对照组。所有受试者均接受心脏彩超获得相关参数[左心房内径(LAD)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室短轴缩短率(LVFS)、左心室后壁厚度(LVPWT)、室间隔厚度(IVST)、左心室射血分数(LVEF)、左心室舒张早期充盈峰最大充盈速度/舒张晚期充盈峰最大峰值速度(E/A)比值、Tei指数],分析心脏彩超相关参数与NYHA分级之间相关性。结果:观察组患者LAD、LVEDD、LVESD、LVPWT、IVST、Tei指数高于对照组(P0.05),LVFS、LVEF、E/A比值低于对照组(P0.05)。Tei指数随着NYHA分级增高而增高(P0.05),LVFS、LVEF、E/A比值随着NYHA分级增高而降低(P0.05)。Spearman秩相关分析结果显示,Tei指数与NYHA分级呈正相关(rs=0.398,P0.05),LVFS、LVEF、E/A比值与NYHA分级呈负相关(rs=-0.285,-0.442,-0.305,P0.05)。结论:高血压LVH伴左心衰竭患者发生明显左室肥厚和左心功能降低,心脏彩超可准确评估高血压LVH伴左心衰竭患者的心功能和病情严重程度,且部分心脏彩超相关参数与NYHA分级相关。     

Left Ventricular Function during Acute High-Altitude Exposure in a Large Group of Healthy Young Chinese Men

Objective

The purpose of this study was to observe left ventricular function during acute high-altitude exposure in a large group of healthy young males.

Methods

A prospective trial was conducted in Szechwan and Tibet from June to August, 2012. By Doppler echocardiography, left ventricular function was examined in 139 healthy young Chinese men at sea level; within 24 hours after arrival in Lhasa, Tibet, at 3700 m; and on day 7 following an ascent to Yangbajing at 4400 m after 7 days of acclimatization at 3700 m. The resting oxygen saturation (SaO2), heart rate (HR) and blood pressure (BP) were also measured at the above mentioned three time points.

Results

Within 24 hours of arrival at 3700 m, the HR, ejection fraction (EF), fractional shortening (FS), stroke volume (SV), cardiac output (CO), and left ventricular (LV) Tei index were significantly increased, but the LV end-systolic dimension (ESD), end-systolic volume (ESV), SaO2, E/A ratio, and ejection time (ET) were significantly decreased compared to the baseline levels in all subjects. On day 7 at 4400 m, the SV and CO were significantly decreased; the EF and FS Tei were not decreased compared with the values at 3700 m; the HR was further elevated; and the SaO2, ESV, ESD, and ET were further reduced. Additionally, the E/A ratio was significantly increased on day 7 but was still lower than it was at low altitude.

Conclusion

Upon acute high-altitude exposure, left ventricular systolic function was elevated with increased stroke volume, but diastolic function was decreased in healthy young males. With higher altitude exposure and prolonged acclimatization, the left ventricular systolic function was preserved with reduced stroke volume and improved diastolic function.     

黄芪甲甙对急性心肌梗死大鼠心室重构和NOX/ROS/TNF⁃α信号通路的影响

研究旨在探究黄芪甲甙对急性心肌梗死大鼠心室重构的作用及其机制。选取36只Wistar大鼠随机分为假手术组、模型组、黄芪甲甙低剂量组、黄芪甲甙中剂量组、黄芪甲甙高剂量组和阳性对照组,每组6只。除假手术组外,其余大鼠手术建立急性心肌梗死模型,假手术组大鼠开胸后仅分离冠状动脉左前降支,不做结扎处理便逐层缝合,造模后第2天开始药物干预：黄芪甲甙低、中、高剂量组分别给予20、40、60 mg·kg^-1黄芪甲甙灌胃处理,阳性对照组给予100 mg·kg^-1阿司匹林灌胃处理。比较各组治疗第0、2、4周心功能指标[左心室射血分数（left ventricular ejection fractions,LVEF）、左心室短轴缩短率（left ventricular fractional shortening,LVFS）、左心室质量指数（left ventricular mass index,LVMI）]的变化情况。采用心脏血流动力学监测系统监测心脏血流动力学指标[左心室舒张末压（left ventricular end diastolic pressure,LVEDP）、左心室收缩压（left ventricular systolic pressure,LVSP）和左心室等容收缩/舒张压上升最大速率（maximal rate of left ventricular pressure increase/decrease,±dp/dt_max）]的变化情况,采用酶联免疫吸附法测定血清血管紧张素Ⅱ（angiotensin Ⅱ,AngⅡ）、内皮素1（endothelin-1,ET-1）、脑钠肽（brain natriuretic peptide,BNP）含量,试剂盒检测心肌组织活性氧（reactive oxygen species,ROS）含量,实时荧光定量PCR和Western blot检测大鼠心肌组织NADPH氧化酶（reduced nicotinamide adenine dinucleotide phosphate oxidase,NOX）、肿瘤坏死因子α（tumor necrosis factor α,TNF-α）mRNA相对表达量和蛋白表达水平。结果显示,治疗4周后,黄芪甲苷高剂量组和阳性对照组LVEF、LVFS随着治疗时间延长不断升高（P<0.05）;与相同治疗时间假手术组比较,模型组LVEF、LVFS均显著降低（P<0.05）;与治疗第0周模型组比较,各治疗组LVEF、LVFS差异无统计学意义（P>0.05）;治疗第2、4周与模型组比较,黄芪甲苷中剂量组、黄芪甲苷高剂量组和阳性对照组LVEF、LVFS显著升高（P<0.05）;与模型组比较,黄芪甲苷中剂量组、黄芪甲苷高剂量组和阳性对照组LVMI显著降低（P<0.05）,LVSP、LVEDP、±dp/dt显著升高（P<0.05）,血清AngⅡ、ET-1、BNP显著降低（P<0.05）,心肌组织ROS含量显著降低（P<0.05）,NOX、TNF-α基因和蛋白表达量显著降低。研究结果表明,黄芪甲甙可改善AMI大鼠心功能和血流动力学紊乱,抑制心室重构,可能与下调NOX/ROS/TNF-α信号通路表达有关。     

苯巴比妥钠联合脑苷肌肽治疗新生儿缺氧缺血性脑病的疗效及对患儿血清HIF-1α、LXA4、ET-1表达的影响

目的:探讨苯巴比妥钠联合脑苷肌肽治疗新生儿缺氧缺血性脑病的疗效及对患儿血清缺氧诱导因子-1α(HIF-1α)、血脂氧素A4(LXA4)、内皮素-1(ET-1)表达的影响。方法:选择2013年1月至2018年3月我院接诊的88例缺氧缺血性脑病新生儿作为本研究对象,将其按照随机数表法分为试验组45例和对照组43例。对照组在常规治疗基础上给予脑苷肌肽注射液2 mL加入0.9%氯化钠溶液50 mL中静脉滴注,1次/d;试验组在对照组基础上给予苯巴比妥钠注射液肌肉注射,首次剂量10 mg/kg/次,24 h内可重复给药2~3次,24 h总剂量最高不超过30 mg/kg,之后以5 mg/kg/d的维持剂量,分2次使用,均连续治疗14 d。比较2组的临床疗效、临床症状恢复时间、治疗前后血清HIF-1α、LXA4、ET-1水平、神经行为评分(NBNA)、心理运动发育指数(PDI)、智力发育指数(MDI)的变化及不良反应的发生情况。结果:治疗后,试验组临床疗效总有效率为93.33%,显著高于对照组(76.74%,P<0.05),原始反射、肌肉张力、意识障碍恢复时间均明显短于对照组(P<0.05),血清HIF-1α、ET-1水平均明显低于对照组,而血清LXA4水平、NBNA评分、PDI评分、MDI评分明显高于对照组(P<0.05)。两组治疗期间均未有发热、皮疹、肝肾功能障碍等不良反应发生。结论:苯巴比妥钠联合脑苷肌肽治疗新生儿缺氧缺血性脑病疗效明显优于脑苷肌肽治疗,其可有效调节血清HIF-1α、LXA4、ET-1水平,促进神经功能恢复,且安全性高。     

Novel function of Roxadustat (FG-4592) as an anti-shock drug in sepsis by regulating mitochondrial oxidative stress and energy metabolism

BackgroundSeptic shock is a serious clinical syndrome leading to high mortality. A new anti-anemia drug Roxadustat (FG-4592) protected against cardiac injury and hypertension. However, its effect and mechanism on shock and cardiac dysfunction induced by sepsis require to be investigated.MethodsC57BL/6j mice received FG-4592 (10 mg/kg/day) by i.p injection, followed by lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) treatment. Mortality and shock status were monitored during the experiment. Cardiac function was assessed using echocardiography and serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) assay. TEM, COX-SDH staining and ATP production were used to evaluate mitochondrial function. A non-targeted metabolomic analysis was performed to evaluate the metabolic disorders.ResultsBoth pre- and post-treatment of FG-4592 could improve the survival rate in LPS- and CLP-induced sepsis mice with a better effect in pre-treated animals. Meanwhile, FG-4592 improved systolic blood pressure and body temperature drop in septic mice along with alleviated cardiac dysfunction (as shown by the restoration of decreased LVEF and LVFS and increased LDH and CK-MB) and inflammation. Interestingly, we observed that FG-4592 improved mitochondrial oxidative stress possibly by upregulating the anti-oxidative enzymes of SOD2 and HO-1. Furthermore, FG-4592 improved the energy supply and glycerophospholipid metabolism in cardiomyocytes, possibly through upregulating the HIF-1α-targeted genes of LDHA and PDK1 in glycolysis and CHK-α, respectively.ConclusionsFG-4592 protected against mortality and shock in septic animals possibly by antagonizing mitochondrial oxidative stress and metabolic disorders.General significanceThis study provides a potential of FG-4592 as a novel drug for treating septic shock.     

Isoprostanes induce plasma extravasation in rat skin

Isoprostane E2 (8-iso PGE) and isoprostane F2 alpha (8-iso PGF) contribute to numerous vascular, proinflammatory, and nociceptive functions. The underlying mechanisms for many of their actions are still under investigation. We examined the ability of isoprostanes to promote cutaneous inflammation using the Evan's blue dye method. Our data show that 4 micrograms subcutaneously (s.c.) injected 8-iso PGE or 8-iso PGF induced plasma extravasation in glabrous rat skin. Dye extravasation was also elicited in hairy skin after injections of 8-iso PGE, but not after 8-iso PGF. Isoprostane-evoked dye extravasation can be reduced by pretreatment with both the S+ and R- isomers of the cyclooxygenase (COX)-inhibitor ibuprofen (30 mg/kg intraperitoneally), indicating perhaps a nonspecific inhibition; pretreatment with ketorolac (1 and 10 mg/kg i.v.) was without effect. Unlike isoprostane-induced cutaneous nociceptor sensitization, which is blocked in a stereospecific and dose-dependent manner by COX-inhibitors, the effect of these drugs on isoprostane-induced cutaneous plasma extravasation is less consistent. We conclude that at least a large component of the isoprostane effect on cutaneous plasma extravasation is COX-independent.     

Hypoxia inducible factor-1 alpha correlates the expression of heme oxygenase 1 gene in pulmonary arteries of rat with hypoxia-induced pulmonary hypertension

AbstractTo test the hypothesis that hypoxia inducible factor-1 alpha (HIF-1α）up-regulated theexpression of heme oxygenase-1 (HO-1) gene in pulmonary arteries of rats with hypoxia-induced pulmonaryhypertension, 8 male Wistar rats in each of 5 groups were exposed to hypoxia for 0, 3, 7, 14 or 21 d, respectively.Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle hypertrophy index weremeasured. Lungs were inflation fixed for immunohistochemistry, in situ hybridization; frozen for latermeasurement of HO-1 enzyme activity, mPAP increased significantly after 7 d of hypoxia [(18.4 ± 0.4)mmHg, P<0.05], reaching its peak after 14 d of hypoxia, then remained stable. Pulmonary artery remodeling became to develop significantly after 14 d of hypoxia. HIF-1αprotein in control was poorly positive (0.05 ±0.01), but was up-regulated in pulmonary arterial tunica intima of all hypoxic rats. In pulmonary arterialtunica media, the levels of HIF-la protein were markedly up-regulated after 3 d and 7 d of hypoxia(0.20±0.02; 0.22 ± 0.02, P<0.05), then declined after 14 d and 21 d of hypoxia. HIF-mRNA stainingwas poorly positive in control, hypoxia for 3 and 7 d, but enhanced significantly after 14 d of hypoxia(0.20±0.02, P<0.05), then remained stable. HO-1 protein increased after 7 d of hypoxia (0.10±0.01,P<0.05), reaching its peak after 14 d of hypoxia (0.21 0.02, P<0.05), then remained stable. HO-1 mRNA increased after 3 d of hypoxia, reaching its peak after 7 d of hypoxia (0.17 ± 0.01, P<0.05), then declined.Linear correlation analysis showed that HIF-lα mRNA, HO-1 protein and mPAP were associatedwith pulmonary remodeling. HIF-1 α protein (tunica intima) was conversely correlated with HIF-1α mRNA(r=0.921, P<0.01), HO-1 protein was conversely correlated with HIF-1α protein (tunica intima)(r=0.821, P<0.01 ). HIF-1αand HO-1 were both involved in the pathogenesis of hypoxia-induced pulmonaryhypertension in rat. Hypoxia inducible factor-1 alpha correlated the expression of heme oxygenase 1 genein pulmonary arteries of rat with hypoxia-induced pulmonary hypertension.     

氧化应激在高原重体力劳动过程中急性高原反应发生中的作用

目的：观察氧化应激在高原重体力劳动过程中急性高原反应（AHAR）发生中的作用。方法：由低海拔（1500m）快速进入高原（3700m）并从事重体力劳动的男性官兵96名,年龄18～35岁。根据AHAR症状评分,分为重度AHAR组（A组,n=24）、轻中度AHAR组（B组,n=47）和无AHAR组（C组,n=25）,在该高度逗留50d后下撤前及返回低海拔（1500m）后12h、15d分别测定血清8．异前列腺素F2a（8-iso-PGF2a）、超氧化物歧化酶（SOD）、丙二醛（MDA）,并与低海拔（1500m）50名健康官兵（D组）比较。结果：A组血清8-iso-PGF2a、MDA[分别为（9．53±0．47）μg／L、（8．91±0．39）μmol／L]水平显著高于B组[分别为（8．34±O．42）μg／L、（7．31±0．32）μmol／L]、C组[分别为（7．02±0．48）μg／L、（6．41±0．23）μmol／L和D组[分别为（5．13±0．56）μg／L、（5．48±0．33）μmol／L]（均P〈0．01）,SOD（52．08±3．44）μ／mL水平显著低于B组（62．27±2．54）μ/mL、C组（71．99±3．35）μ/mL和D组（80．78±3．44）μ/mL,（均P〈0．01）,B组与c组之间和C组与D组之间亦有显著性差异（均P〈0．01）。海拔3700mAHAR总计分与血清8-iso-PGF2α、ⅣⅡ）A呈显著正相关（均P〈0．01）,与血清SOD显著负相关（P〈0．01）;8-iso-PGF2α、MDA与SOD显著负相关（均P〈0．01）。海拔3700m50d,血清8-iso-PGF2α、MDA水平显著高于,SOD水平显著低于海拔1500m12h、15d和D组（均P〈0．01）,海拔1500m12h与15d之间有显著性差异（均P〈0．01）,海拔1500m 15d与D组之间无显著性差异。结论：人体在高原低氧并重体力时氧化应激和氧化．抗氧化失衡与AHAR的发病和程度有密切关系,氧化应激和氧化．抗氧化失衡越严重,AHAR越重。返回低海拔后12h有显著改善,15d恢复到正常水平。     

Administration of prostaglandin f(2 alpha) during the early bovine luteal phase does not alter the expression of ET-1 and of its type A receptor: a possible cause for corpus luteum refractoriness

Luteal regression is initiated by prostaglandin F(2 alpha) (PGF(2 alpha)). In domestic species and primates, demise of the corpus luteum (CL) enables development of a new preovulatory follicle. However, during early stages of the cycle, which are characterized by massive neovascularization, the CL is refractory to PGF(2 alpha). Our previous studies showed that endothelin-1 (ET-1), which is produced by the endothelial cells lining these blood vessels, plays a crucial role during PGF(2 alpha)-induced luteolysis. Therefore, in this study, we compared the effects of PGF(2 alpha) administered at the early and mid luteal phases on ET-1 and its type A receptors (ETA-R) along with plasma ET-1 and progesterone concentrations, and the mRNA levels of PGF(2 alpha) receptors (PGF(2 alpha)-R) and steroidogenic genes. As expected, ET-1 and ETA-R mRNA levels were markedly induced in midcycle CL exposed to luteolytic dose of PGF(2 alpha) analogue (Cloprostenol). In contrast, neither ET-1 mRNA nor its receptors were elevated when the same dose of PGF(2 alpha) analogue was administered on Day 4 of the cycle. In accordance with ET-1 expression within the CL, plasma ET-1 concentrations were significantly elevated 24 h after PGF(2 alpha) injection only on Day 10 of the cycle. The steroidogenic capacity of the CL (plasma progesterone as well as the mRNA levels of steroidogenic acute regulatory protein and cytochrome P450(scc)) was only affected when PGF(2 alpha) was administered during midcycle. Nevertheless, PGF(2 alpha) elicited certain responses in the early CL: progesterone and oxytocin secretion were elevated, and PGF(2 alpha)-R was transiently affected. Such effects probably result from PGF(2 alpha) acting on luteal steroidogenic cells. These findings may suggest, however, that the cell type mediating the luteolytic actions of PGF(2 alpha), possibly the endothelium, could yet be nonresponsive during the early luteal phase.     

Real-time relationships in intraluteal release among Prostaglandin F2alpha, endothelin-1, and angiotensin II during spontaneous luteolysis in the cow

It is well known that prostaglandin F(2alpha) (PGF(2alpha)) is a physiological luteolysine, and that its pulsatile release from the endometrium is a luteolytic signal in many species. There is now clear evidence that the vasoactive peptides endothelin-1 (ET-1) and angiotensin II (Ang II) interact with PGF(2alpha) in the luteolytic cascade during PGF(2alpha)-induced luteolysis in the cow. Thus, we investigated the local secretion of PGF(2alpha), ET-1, and Ang II in the corpus luteum (CL) and their real-time relationships during spontaneous luteolysis in the cow. For this purpose, an in vivo microdialysis system (MDS) implanted in the CL was utilized to observe local secretion changes within the CL microenvironment. Each CL of cyclic Holstein cows (n = 6) was surgically implanted with MDS capillary membranes (18 lines/6 cows) on Day 15 (estrus = Day 0) of the estrous cycle. The concentrations of PGF(2alpha), ET-1, Ang II, and progesterone (P) in the MDS samples were determined by enzyme immunoassays. The intraluteal PGF(2alpha) secretion slightly increased from 12 h after the onset of luteolysis (0 h) and drastically increased (by about 300%) from 24 h. Intraluteal ET-1 secretion increased from 12 h. Intraluteal Ang II secretion was elevated from 0 h and was maintained at high levels (about 180%) toward estrus. In each MDS lines (in the same microenvironment) within the regressing CL, the local releasing profiles of PGF(2alpha), ET-1, and Ang II CL positively correlated with each other (P < 0.05) at high proportions in 18 MDS lines (PGF(2alpha) vs. ET-1, 44.4%; PGF(2alpha) vs. Ang II, 55.6%; ET-1 vs. Ang II, 38.9%). In contrast, there was no clear relationship among these substances released into different MDS lines implanted in the same CL (with different microenvironments). In conclusion, we propose that the increase of PGF(2alpha), ET-1, and Ang II within the CL during luteolysis is a common phenomenon for both PGF(2alpha)-induced and spontaneous luteolysis. Moreover, this study illustrated the in vivo relationships in intraluteal release among PGF(2alpha), ET-1, and Ang II during spontaneous luteolysis in the cow. The data suggest that these vasoactive substances may interact with each other in a local positive feedback manner to activate their secretion in the regressing CL, thus accelerating and completing luteolysis.     

The role of oxygen-increased respirator in humans ascending to high altitude

ABSTRACT: BACKGROUND: Acute mountain sickness is common for people who live in low altitude areas ascending to the high altitude. Many instruments have been developed to treat mild cases of AMS. However, long-lasting and portable anti-hypoxia equipment for individual is not yet available. METHODS: Oxygen-increased respirator (OIR) has been designed to reduce the risk of acute mountain sickness in acute exposure to low air pressure. It can increase the density of oxygen by increasing total atmospheric pressure in a mask. Male subjects were screened, and eighty-eight were qualified to perform the experiments. The subjects were divided into 5 groups and were involved in some of the tests at 4 different altitudes (Group 1, 2: 3700 m Group 3,4,5: 4000 m, 4700 m, 5380 m) with and without OIR. These tests include heart rate, saturation of peripheral oxygen (SpO2), malondialdehyde (MDA), superoxide dismutase (SOD), blood lactate (BLA) and PWC (physical work capacity) -170. RESULTS: The results showed that higher SpO2, lower heart rate (except during exercise) and better recovery of heart rate were observed from all the subjects 'with OIR' compared with 'without OIR' (P < 0.05). Moreover, compared with 'without OIR', subjects 'with OIR' in Group 1 had lower concentrations of MDA and BLA, and a higher concentration of SOD (P < 0.05), while subjects 'with OIR' in Group 2 showed better physical capacity (measured by the PWC-170) (P < 0.05). The additonal experiment conducted in a hypobaric chamber (simulating 4,000 m) showed that the partial pressure of oxygen in blood and arterial oxygen saturation were higher 'with OIR' than 'without OIR' (P < 0.05). CONCLUSIONS: We suggested that OIR may play a useful role in protecting people ascending to high altitude before acclimatization.     

B-type natriuretic peptide, vascular endothelial growth factor, endothelin-1, and nitric oxide synthase in chronic mountain sickness

The pathogenesis of chronic mountain sickness (CMS) may involve vasoactive peptides. The aim of this study was to investigate associations between CMS and levels of B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS). A total of 24 patients with CMS and 50 control subjects residing at 4,300 m participated in this study. Mean pulmonary arterial pressure (mPAP) was measured by echocardiography. Serum BNP, VEGF, ET-1, and eNOS were measured. Receiver operator characteristic curves to assess the balance of sensitivity and specificity for CMS were constructed. As a result, patients with CMS had significantly greater mPAP compared with controls and had lower arterial O(2) saturation (Sa(O(2))). Both BNP and ET-1 correlated positively with mPAP and negatively with Sa(O(2)), whereas serum VEGF levels were inversely correlated with Sa(O(2)); eNOS correlated negatively with mPAP and positively with Sa(O(2)). Median concentrations of BNP were greater in patients with CMS compared with those without CMS: 369 pg/ml [interquartile range (IQR) = 336-431] vs. 243 pg/ml (IQR = 216-279); P < 0.001. Similarly, concentrations of VEGF [543 pg/ml (IQR = 446-546) vs. 243 pg/ml (IQR = 216-279); P < 0.001] and ET-1 [14.7 pg/ml (IQR = 12.5-17.9) vs. 11.1 pg/ml (IQR = 8.7-13.9); P = 0.05] were higher in those with CMS compared with those without, whereas eNOS levels were lower in those with CMS [8.90 pg/ml (IQR 7.59-10.8) vs. 11.2 pg/ml (9.13-13.1); P < 0.001]. The areas under the receiver operator characteristic curves for diagnosis of CMS were 0.91, 0.93, 0.77, and 0.74 for BNP, VEGF, ET-1, and eNOS, respectively. In age- and biomarker-adjusted logistic regression, BNP and VEGF were positively predictive of CMS, whereas eNOS was inversely predictive. In conclusion, severe chronic hypoxemia and consequent pulmonary hypertension in patients with CMS may stimulate release of natriuretic peptides and angiogenic cytokines. These vasoactive peptides may play an important role in the pathogenesis and clinical expression of CMS and may indicate potential prognostic factors in CMS that could serve as targets for therapeutic trials or clinical decision making.     

Ventilatory chemosensitive adaptations to intermittent hypoxic exposure with endurance training and detraining.

The present study was performed to clarify the effects of intermittent exposure to an altitude of 4,500 m with endurance training and detraining on ventilatory chemosensitivity. Seven subjects (sea-level group) trained at sea level at 70% maximal oxygen uptake (VO2 max) for 30 min/day, 5 days/wk for 2 wk, whereas the other seven subjects (altitude group) trained at the same relative intensity (70% altitude VO2 max) in a hypobaric chamber. VO2 max, hypoxic ventilatory response (HVR), and hypercapnic ventilatory response, as an index of central hypercapnic chemosensitivity (HCVR) and as an index of peripheral chemosensitivity (HCVRSB), were measured. In both groups VO2 max increased significantly after training, and a significant loss of VO2 max occurred during 2 wk of detraining. HVR tended to increase in the altitude group but not significantly, whereas it decreased significantly in the sea-level group after training. HCVR and HCVRSB did not change in each group. After detraining, HVR returned to the pretraining level in both groups. These results suggest that ventilatory chemosensitivity to hypoxia is more variable by endurance training and detraining than that to hypercapnia.     

藏羚羊低氧诱导因子1α基因的克隆与组织表达

为探讨低氧诱导因子1α (hypoxia inducible factor l alpha,HIF-1α)在藏羚羊(Pantholops hodgsonii)高原低氧适应机制中的作用,采用RT-PCR和RACE技术克隆藏羚羊HIF-1α基因的cDNA序列,同时采用real-time PCR和Western blot方法...     

高原健康居民某些内分泌激素的变化及其生理意义

本文在海拔10m(青岛)、2260m(青海西宁)和3700m(青海玉树)三个高度,用放射免疫法,测定445例健康人血四碘甲腺原氨酸(T_4)、三碘甲腺原氨酸(T_3)、3,3’,5’三碘甲腺原氨酸(rT3)皮质醇(F)和醛固酮(ALD)含量。结果发现:(1)高海拔地区世居藏族与有15年以上移居史的汉族居民五项测值间无显著差别(P>0.05);(2)高海拔地区居民T_3、T_4、F和ALD含量降低(P<0.05～0.001),而rT3则升高(P<0.01)。这些变化的生理意义,可能反映了高原居民对低氧环境的一种慢性适应机制。在某些高原疾病防治中,适当应用肾上腺皮质激素,可能有一定临床价值。     

Reversal of hypoxia-induced decrease in human cardiac response to isoproterenol infusion

A decrease in heart rate response to isoproterenol (IP) infusion has been previously described in humans exposed to acute (2-3 days) or chronic (21 days) exposure to altitude hypoxia (J. Appl. Physiol. 65: 1957-1961, 1988). To evaluate this cardiac response in subacute (8 days) hypoxia and to explore its reversal with restoration of normoxia, six subjects received an IP infusion under normoxia (condition N), after 8 days in altitude (4,350 m, condition H8), on the same day in altitude after inhalation of O2 restoring normoxic arterial O2 saturation (SaO2, condition HO), and 6-11 h (condition RN) and 4-5 mo (condition ND) after the return to sea level. Cardiac chronotropic response to IP, evaluated by the mean increase in heart rate from base value (delta HR, min-1), was lower in condition H8 [mean 30 +/- 13 (SD)] than in condition N (50 +/- 14, P less than 0.03); it was slightly higher in condition HO (38 +/- 14) or condition RN (42 +/- 15) than condition H8 but still significantly different from condition N (P less than 0.03), despite normal values of SaO2. delta HR in condition ND (55 +/- 10) returned to base N value. These findings confirm the hypothesis of a hypoxia-induced decrease in cardiac chronotropic function. Two possible mechanisms are suggested: an O2-dependent one, rapidly reversible with recent restoration of normoxia, and a more slowly reversible mechanism, probably a downregulation of the cardiac beta-receptors.     

Hypoxia Induces Transforming Growth Factor-β1 Gene Expression in the Pulmonary Artery of Rats via Hypoxia-inducible Factor-1α

The present study was undertaken to investigate the dynamic expression of hypoxia induciblefactor-1 α (HIF-1α) and transforming growth factor-β1 (TGF-β1) in hypoxia-induced pulmonary hypertensionof rats.It was found that mean pulmonary arterial pressure (mPAP) increased significantly after 7 d ofhypoxia.Pulmonary artery remodeling index and right ventricular hypertrophy became evident after 14 d ofhypoxia.HIF-1α mRNA staining was less positive in the control,hypoxia for 3 d and hypoxia for 7 d,butbegan to enhance significantly after 14 d of hypoxia,then remained stable.Expression of HIF-1 α protein inthe control was less positive,but was up-regulated in pulmonary arterial tunica intima of all hypoxic rats.TGF-β1 mRNA expression in pulmonary arterial walls was increased significantly after 14 d of hypoxia, butshowed no obvious changes after 3 or 7 d of hypoxia.In pulmonary tunica adventitia and tunica media,TGF-β1 protein staining was less positive in control rats,but was markedly enhanced after 3 d of hypoxia,reaching its peak after 7 d of hypoxia,and then weakening after 14 and 21 d of hypoxia.Western blottingshowed that HIF- 1α protein levels increased significantly after 7 d of hypoxia and then remained at a highlevel. TGF-β1 protein level was markedly enhanced after 3 d of hypoxia,reaching its peak after 7 d ofhypoxia,and then decreasing after 14 and 21 d of hypoxia.Linear correlation analysis showed that HIF-1αmRNA, TGF-β1 mRNA, TGF-β1 protein were positively correlated with mPAP,vessel morphometry andright ventricular hypertrophy index.TGF-β1 protein (tunica adventitia) was negatively correlated withHIF-lα mRNA.Taken together,our results suggest that changes in HIF-lα and TGF-β1 expression afterhypoxia play an important role in hypoxia-induced pulmonary hypertension of rats.