Heliox and oxygen reduce infarct volume in a rat model of focal ischemia

Normobaric hyperoxia treatment has recently been demonstrated to be remarkably beneficial in acute focal ischemia. The present study compared hyperoxia treatment with a novel heliox treatment. Adult male rats breathed 30% oxygen and 70% nitrogen (control group), 100% oxygen (hyperoxia group), or 30% oxygen and 70% helium (heliox group) during a middle cerebral artery occlusion for 2 h and a 1-hour reperfusion (n=6 in each group). Neurological deficits were scored at 3 and 24 h post focal ischemia. Neither the physiological parameters (body temperature, blood pressure, heart rate, O(2) saturation, and laser Doppler cerebral blood) nor the 3-hour post ischemia neurological scores differed between groups. However, the neurological scores showed a statistically significant improvement at 24 h post ischemia in the heliox group (p<0.05). The infarct volume (mean+SD) as measured by 2,3,5-triphenyltetrazolium staining included 36+/-17% of the involved hemisphere in the control group, 16+/-14% in the hyperoxia group, and 4+/-2% in the heliox group (p<0.01). In conclusion, whereas hyperoxia reduced the infarct volume, heliox further reduced the infarct volume and improved 24-hour neurological deficits in a rat model of focal ischemia. This suggests that a greater benefit may accrue from heliox therapy.     

经胃灌入高氧液对油酸型急性肺损伤家兔的治疗效果

目的 研究经胃灌人高氧液(HO)对油酸型急性肺损伤(ALI)家兔的治疗作用.方法 以复方氯化钠为基液制备HO.将1 8只家兔随机均分为油酸致伤组(A组)、HO治疗组(B组)和正常对照组(C组).A、B组均经耳缘静脉注入油酸0.06 ml/kg建立ALI模型,C组注入等量生理盐水.B组于注射油酸30 min时经胃灌入HO 20 ml/kg,A、C组灌入等量复方氯化钠.各组分别在ALI模型制备前(0min)、注射油酸后30、60、120 min经右颈外动脉抽血进行血气分析,并测定肺水含量、肺体比值及病理榆查.结果 与C组相比,人组PaO2,PaCO2明显降低(P＜0.01),肿水含量、肺体比值及肺损伤评分明、显增高(P＜0.01).镜下见肺灶性出血,间质、肺泡水肿,大量炎性细胞浸润.B组经HO治疗后迅速提升PaO2.PaCO2(P＜0.05),减轻肺水肿(P＜0.01).结论 经胃灌人HO对油酸型ALI家兔有治疗作用.     

常压高氧疗法在危重病中的应用

缺氧可致机体损害,过多的氧也会导致生理功能紊乱和脏器功能损害,称为氧中毒。危重患者的治疗需要积极、主动、最大限度地提升氧分压,挽救受累的组织器官,改善预后。由于高压氧治疗在危重病领域受到限制,很多学者由基础到临床,从氧中毒的机制、监测和药物预防对常压高氧治疗进行多渠道、多角度的探索,力求通过早期、安全、有效地供氧来满足机体的需要。临床上对高浓度氧疗仍存在许多误区和不足,有必要评估常压高氧在危重病治疗中的功与过。     

Multiple-organ effect of normobaric hyperoxia in neonatal rats

PURPOSE: Prolonged exposure to normobaric hyperoxia (NH) is associated with blood leukocyte activation and sequestration in the lung. Whether NH-induced leukocyte activation and sequestration can affect extrapulmonary organs or blood cellular profile has not been systematically investigated. We studied simultaneous changes in blood cellular profile and pulmonary, renal, and intestinal histology during NH and after return to air breathing ("weaning"). MATERIALS AND METHODS: One-day-old rats were exposed to 2 to 4 days of NH (FiO2 >0.98) or normoxia (FiO2 = 0.21), with or without weaning. Pups were then euthanized and 100 microL of blood was collected (cardiac puncture) for differential white blood cells analysis (n = 12 per group). The lungs, a piece of distal ileum, and the left kidney were removed for histologic evaluation. RESULTS: Both NH and weaning generated significant increases in blood neutrophil count, whereas lymphocyte population was significantly increased only after weaning (P < .05; analysis of variance with Bonferroni correction for multiple comparisons). Normobaric hyperoxia created mild increases in the renal tubular necrosis, dilation, regeneration, and interstitial inflammation. A significant increase in the intestinal serosal and submucosal vasodialation and vascularization occurred 1 day after weaning from 4 days of NH (P < .001). These extrapulmonary events coincided with the development of histologic manifestations of pulmonary oxygen toxicity. CONCLUSIONS: Development of pulmonary oxygen toxicity in neonatal rats is associated with significant changes in differential leukocyte counts and histologic alterations in the kidney and ileum. We speculate that activation of circulating leukocytes and/or direct effect of NH may affect certain peripheral organs independently from the NH-induced pulmonary pathology.     

Hyperoxia exaggerates bacterial dissemination and lethality in Pseudomonas aeruginosa pneumonia

Effects of hyperoxia on lethality in mice with Pseudomonas aeruginosa pneumonia were defined, and protective roles of macrolides were examined both in vitro and in vivo. Sub-lethal hyperoxia accelerated lethality of mice with P. aeruginosa pneumonia. Bacterial number was not different in the lungs, but higher in the liver of mice in hyperoxic conditions. Filter-sterilized culture supernatants of bacteria induced loss of viability of alveolar epithelial cells, which was exaggerated in hyperoxia. Metalloprotease blocking by inhibitor or gene-disruption in bacteria resulted in partial reduction of cytotoxic activity in culture supernatants. Co-culture of bacteria with sub-inhibitory concentrations of macrolides, such as azithromycin, reduced cytotoxic activity in the culture supernatants. Azithromycin provided significant survival benefit in hyperoxia–pneumonia model, which was associated with suppression of bacterial dissemination to extra-pulmonary organs. These results suggest that hyperoxia serves as an important cofactor for bacterial dissemination and lethality of P. aeruginosa pneumonia. Our data identify the potential of macrolides to protect individuals with P. aeruginosa pneumonia in the setting of hyperoxia.     

肺表面活性物质对大鼠高氧性肺损伤的影响

目的探讨肺表面活性物质(PS)在大鼠高氧性肺损伤中的作用。方法将大鼠随机分为3组:高氧组、高氧+PS组、空气氧组。HE染色观察肺组织形态结构;检测支气管肺泡灌洗液(BALF)中肿瘤坏死因子(TNF-α)浓度;肺组织匀浆液中丙二醛(MDA)浓度。结果PS组BALF中TNF-α浓度及肺组织匀浆液中MDA浓度均较高氧组低,两组比较具有显著性差异;高氧组肺组织有严重的毛细血管阻塞和血管周围水肿及白细胞浸润,肺泡间隔明显增厚;PS组有轻微的毛细血管阻塞和血管周围轻度水肿及少量的白细胞浸润,肺泡间隔轻度增厚。结论PS对大鼠高氧性肺损伤有减轻和保护作用,其机理可能与PS具有抗氧化损伤作用有关。     

结缔组织生长因子在高氧致早产鼠慢性肺疾病中的表达及其作用

目的：肺纤维化是高氧致慢性肺疾病(chroniclungdiseases,CLD)的最终结局,结缔组织生长因子(connectivetissuegrowthfactor,CTGF)是近年来发现的与纤维化形成密切相关的因子,但其在CLD肺纤维化中的作用目前尚未见报道。该实验旨在研究CTGF在高氧致CLD中的动态表达规律,并探讨其在CLD中的作用。方法：将50例早产鼠随机分为实验组(高氧组)和对照组(空气组),分别于建立模型后1,3,7,14,21d应用免疫组化技术动态检测肺组织中CTGF的表达部位和强度,对肺组织纤维化程度进行病理组织学评分。结果：对照组小鼠CTGF仅在血管内皮细胞、支气管、细支气管上皮细胞有微弱表达;实验组于建立模型后1,3,7d表达部位与对照组相似,表达强度与对照组无差异(P>0.05),14d表达增强(P<0.01),在部分肺上皮细胞、肺泡间隔、成纤维细胞中出现表达,21d表达明显增强(P<0.01)。高氧组14d和21dCTGF表达水平与肺组织纤维化程度呈明显正相关(分别为r=0.903,r=0.926,均P<0.01)。结论：随着高氧暴露时间的延长和纤维化的发展,CTGF表达增强,其与高氧所致CLD肺纤维化的发生密切相关。     

高氧致新生鼠急性肺损伤及氧化应激反应的动态研究

目的研究新生鼠暴露于高浓度氧不同时间后肺组织的病理改变,以及肺组织氧化应激反应状况。方法新生鼠暴露于>95%O2和正常空气(21%O2)中,取暴露12、24、48和72 h 4个时相点的肺组织,观察其病理变化,检测肺组织匀浆中丙二醛(malondiadehyde,MDA)含量、总抗氧化能力(total anti-oxygen capability,TAOC)。结果新生鼠暴露于>95%O212 h即可引起肺组织损伤,肺组织MDA含量显著升高(P<0.01),TAOC显著降低(P<0.01);随着氧暴露时间延长,MDA含量逐渐增高,TAOC逐渐降低,肺损伤加重,肺组织病理学检查可见肺组织微血管扩张、充血,肺泡内蛋白渗出,炎症细胞浸润,肺组织结构紊乱,肺大泡数量增多,II型肺泡上皮细胞脱落等。结论新生鼠暴露于>95%O212 h即可导致肺损伤和肺组织氧化应激反应的发生,高氧肺损伤与肺组织氧化应激反应有关。     

维甲酸通过MAPKs信号通路减轻早产大鼠AECⅡ高氧性损伤

 目的： 探讨高氧暴露对原代培养的早产大鼠肺泡Ⅱ型上皮细胞（AECⅡ）增殖和凋亡的影响以及维甲酸（RA）的保护作用机制。方法：建立原代培养的早产大鼠高氧暴露AECⅡ模型，采用流式细胞术（Annexin V-PI双标记）检测AECⅡ凋亡，Western blotting检测其磷酸化和总的ERK1/2、JNK1/2和p38表达以及增殖细胞核抗原（PCNA）和caspase-3表达。结果：高氧暴露12 h，Annexin Ⅴ（+）PI（-）和Annexin Ⅴ（+）PI（+）标记的AECⅡ数均显著高于空气组（P<0.01），RA具有明显下调作用；同时，高氧暴露显著提高AECⅡ 磷酸化ERK1/2、JNK1/2和p38表达以及caspase-3活性片段表达（P<0.01），明显降低其PCNA表达（P<0.01）；RA则显著下调高氧暴露下AECⅡ磷酸化JNK1/2和p38表达以及caspase-3活化片段表达（P<0.01），明显提高磷酸化ERK1/2和PCNA表达（P<0.01）。结论：高氧暴露，导致AECⅡ大量凋亡、坏死，增殖受到抑制；RA通过下调JNK1/2和p38磷酸化水平、上调ERK1/2磷酸化水平，降低AECⅡ坏死、凋亡，促进其增殖，从而发挥拮抗高氧肺损伤的作用。