c-Jun氨基末端激酶信号转导通路在高体积分数氧肺损伤大鼠中的作用

目的探讨c-Jun氨基末端激酶(JNK)信号转导通路在高体积分数氧(高氧)诱导的肺损伤大鼠中的作用。方法24只3周龄Wistar大鼠随机分为3组(n=8):空气对照组、高氧暴露7d组、高氧暴露7d+JNK抑制剂干预组。高氧暴露组置于吸氧体积分数(FiO2)≥950mL.L-1常压高氧仓中,空气对照组置于同室常压空气中(FiO2=210mL.L-1),JNK抑制剂干预组动物经腹腔注射SP60012530mg·kg-1,2h后再予高氧暴露。光镜下观察各组肺组织病理学改变,并测定肺湿质量/干质量(W/D)、支气管肺泡灌洗液(BALF)蛋白水平和肺通透指数,末端标记法分析肺组织细胞凋亡的变化,蛋白免疫印迹法检测肺组织磷酸化-JNK(p-JNK)蛋白水平。结果与空气对照组比较,高氧暴露7d组肺组织出现明显充血、水肿、出血及大量炎性细胞浸润,肺W/D、BALF蛋白水平、肺通透指数及肺组织细胞凋亡指数和p-JNK蛋白水平均显著增加(Pa<0.05)。凋亡细胞主要见于小呼吸道和肺泡上皮细胞及血管内皮细胞。高氧暴露7d+JNK抑制剂干预组较高氧暴露7d组肺组织病理损伤及炎性渗出、水肿明显减轻,肺W/D、BALF蛋白水平、肺通透...     

Oxygen: kill or cure? Prehospital hyperoxia in the COPD patient

High concentration oxygen therapy has long been a mainstay of prehospital treatment. Guidelines for its administration have for many years also cautioned its use with patients with chronic obstructive pulmonary disease (COPD).¹ Successive guidelines and prehospital textbooks have advocated the use of 28% oxygen masks and re‐emphasised the importance of the dangers of hyperoxia, often drawing upon the classic theory of hypoxic drive. Despite this, the reality remains that ambulance crews have tended to overoxygenate such patients. One study demonstrated that 80% of patients sampled with acute exacerbation of their COPD received oxygen in excess of 28% from the ambulance crew.² Is this a worrying development or a reassuring sign that prehospital providers are rightly more concerned about the dangers of hypoxia than hyperoxia? And if the guidelines are right, then how are the hearts and minds of ambulance paramedics and technicians won?     

Exercise limb blood flow response to acute and chronic hypoxia in Danish lowlanders and Aymara natives

Aim: The femoral artery blood flow response to submaximal, one‐legged, dynamic, knee‐extensor exercise was determined in acute and chronic hypoxia to investigate the hypotheses that with adaptation to chronic hypoxia blood haemoglobin increases, allowing preservation of blood flow as in normoxia. Methods: Sixteen Danish lowlanders participated, in groups of six to eight, in the experiments at sea level normoxia (FiO₂ ? 0.21) and acute hypoxia (FiO₂ ? 0.11), and chronic hypoxia after ～7 and 9–10 weeks at ～5260 m altitude breathing ambient air (FiO₂ ? 0.21) or a hyperoxic gas (FiO₂ ? 0.55). The response was compared with that in six Aymara natives. Results: The haemoglobin and haematocrit increased (P < 0.003) in the lowlanders at altitude vs. at sea level by ～39 and 27% respectively; i.e. to a similar (P = ns) level as in the natives. At rest, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. During the onset of and incremental exercise, blood flow was the same (P = ns) in the lowlanders at sea level and altitude, as in the natives at altitude. Acute hypoxia increased (P < 0.05) blood flow by ～55% during exercise in the lowlanders at sea level. Acute hyperoxia decreased (P < 0.05) blood flow by ～22–29% during exercise in the lowlanders and natives at altitude. Conclusion: In chronic hypoxia, blood haemoglobin increases, allowing normalization of the elevated exercise blood flow response in acute hypoxia, and preservation of the kinetics and steady‐state exercise blood flow as in normoxia, being similar as in the natives at altitude.     

Effects of hyperoxic ventilation on 6-h survival at the critical haemoglobin concentration aggravated by experimentally induced tachycardia in anaesthetized pigs

Aim: Administration of 100% oxygen [hyperoxic ventilation (HV)] has been proven to ameliorate oxygen transport, tissue oxygenation and survival in different models of extreme normovolemic and hypovolemic anaemia. However, up to date, it is unknown whether HV is also able to improve outcome of extreme anaemia if myocardial oxygen consumption is contemporaneously increased by tachycardia. Therefore, we investigated the influence of HV on the 6‐h survival rate during extreme anaemia and aggravated by experimentally induced tachycardia in a prospective, randomized study in a pig model of critical anaemia. Methods: After government approval, 14 anesthetized pigs mechanically ventilated on room air were haemodiluted by replacing a certain amount of whole blood with hydroxethyl starch 6% (200.000/0.5) until their individual critical haemoglobin concentration (Hb_crit) was achieved. At Hb_crit, tachycardia (180 bpm) was induced in all animals by atrial pacing. Thereafter, animals were observed for the next 6 h either at room air (FiO₂ 0.21; group NOX) or during HV (FiO₂ 1.0; group HOX) without further intervention. As primary outcome parameter of this study, the 6‐h survival rate was selected. Results: Hyperoxic ventilation increased the 6‐h survival rate from 14 to 100%. In contrast to the NOX group, macrohaemodynamics and oxygen transport improved in the HOX group during the observation period without apparent adverse effects of HV. Conclusions: Hyperoxic ventilation can be considered a safe and effective measure for the optimization of oxygen supply during extreme anaemia and despite concomitant tachycardia within 6 h. Whether HV can also be recommended beyond this period warrants further studies.     

体外高氧对人胚肺成纤维细胞增殖、凋亡的影响

目的探讨高氧对体外培养的人胚肺成纤维细胞（HELF）增殖、凋亡的影响。方法将生长良好的HELF传代后,用无血清培养基培养24 h,分别置于空气及90%高氧的细胞培养箱中,培养5 d,绘制细胞生长曲线,免疫组化法检测增殖细胞核抗原（PCNA）蛋白表达,流式细胞术检测细胞凋亡率。结果与空气相比,高氧抑制HELF的增殖,诱导HELF凋亡（P〈0.05或〈0.01）,且随高氧暴露时间延长,呈现明显的时间依赖关系。结论体外高氧对HELF具有明显的抑制细胞增殖和促进细胞凋亡作用。     

雌激素对新生大鼠高氧肺损伤的影响

[目的]探讨雌激素对高氧所诱发新生大鼠肺损伤的影响.[方法]选用生后2d、体重为5～10g的新生Wistar大鼠,雌雄不拘,随机分为空气对照组、高氧模型组及雌激素治疗组.将空气对照组新生大鼠暴露在室内空气中,其他各组新生大鼠暴露在90%(体积分数)氧中共14d,雌激素治疗组新生大鼠每日分别腹腔内注射给予雌激素2mg/kg,空气对照组和高氧模型组腹腔内注射给予生理盐水.实验开始第3,7,14天时间点记录各组新生大鼠自然死亡数目,计算死亡率;每组处死10只,取肺组织,在光学显微镜下观察肺组织的病理变化,采用免疫组织化学染色方法观察肺组织中γ干扰素(IFN-γ)的表达.[结果]随着高氧暴露时间的延长,高氧模型组及雌激素治疗组死亡率均呈增高趋势,高氧模型组暴露7 d后开始死亡率迅速升高,而雌激素治疗组死亡率明显降低,相比较差异具有统计学意义(P<0.05).空气对照组IFN-γ无阳性表达,而高氧模型组中的阳性表达在第7天时达到高峰,第14天时明显下降,但仍高于空气对照组;雌激素治疗组中的IFN-γ表达强度在各时间段均明显低于高氧模型组(P<0.01).[结论]雌激素对新生大鼠高氧肺损伤有保护作用.     

In vivo quantification of hyperoxic arterial blood water T1

Normocapnic hyperoxic and hypercapnic hyperoxic gas challenges are increasingly being used in cerebrovascular reactivity (CVR) and calibrated functional MRI experiments. The longitudinal arterial blood water relaxation time (T_1a) change with hyperoxia will influence signal quantification through mechanisms relating to elevated partial pressure of plasma‐dissolved O₂ (pO₂) and increased oxygen bound to hemoglobin in arteries (Y_a) and veins (Y_v). The dependence of T_1a on Y_a and Y_v has been elegantly characterized ex vivo; however, the combined influence of pO₂, Y_a and Y_v on T_1a in vivo under normal ventilation has not been reported. Here, T_1a is calculated during hyperoxia in vivo by a heuristic approach that evaluates T₁‐dependent arterial spin labeling (ASL) signal changes to varying gas stimuli. Healthy volunteers (n = 14; age, 31.5 ± 7.2 years) were scanned using pseudo‐continuous ASL in combination with room air (RA; 21% O₂/79% N₂), hypercapnic normoxic (HN; 5% CO₂/21% O₂/74% N₂) and hypercapnic hyperoxic (HH; 5% CO₂/95% O₂) gas administration. HH T_1a was calculated by requiring that the HN and HH cerebral blood flow (CBF) change be identical. The HH protocol was then repeated in patients (n = 10; age, 61.4 ± 13.3 years) with intracranial stenosis to assess whether an HH T_1a decrease prohibited ASL from being performed in subjects with known delayed blood arrival times. Arterial blood T_1a decreased from 1.65 s at baseline to 1.49 ± 0.07 s during HH. In patients, CBF values in the affected flow territory for the HH condition were increased relative to baseline CBF values and were within the physiological range (RA CBF = 36.6 ± 8.2 mL/100 g/min; HH CBF = 45.2 ± 13.9 mL/100 g/min). It can be concluded that hyperoxic (95% O₂) 3‐T arterial blood T_1aHH = 1.49 ± 0.07 s relative to a normoxic T_1a of 1.65 s. Copyright © 2015 John Wiley & Sons, Ltd.