Changes in acid-base status in oxygen toxicity at 230 kPa oxygen as a function of exposure time.

Breathing less than 50 kPa of oxygen over time can lead to pulmonary oxygen toxicity (POT). Vital capacity (VC) as the sole parameter for POT has its limitations. In this study we try to find out the changes of acid-base status in a POT rat model. Fifty male rats were randomly divided into five groups, exposed to 230 kPa oxygen for three, six, nine and 12 hours, respectively. Rats exposed to air were used as controls. After exposure the mortality and behavior of rats were observed. Arterial blood samples were collected for acid-base status detection and wet-dry (W/D) ratios of lung tissues were tested. Results showed that the acid-base status in rats exposed to 230 kPa oxygen presented a dynamic change. The primary status was in the compensatory period when primary respiratory acidosis was mixed with compensated metabolic alkalosis. Then the status changed to decompensated alkalosis and developed to decompensated acidosis in the end. pH, PCO2, HCO3-, TCO2, and BE values had two phases: an increase and a later decrease with increasing oxygen exposure time, while PaO2 and lung W/D ratio showed continuously increasing trends with the extension of oxygen exposure time. Lung W/D ratio was significantly associated with PaO2 (r = 0.6385, p = 0.002), while other parameters did not show a significant correlation. It is concluded that acid-base status in POT rats presents a dynamic change: in the compensatory period first, then turns to decompensated alkalosis and ends up with decompensated acidosis status. Blood gas analysis is a useful method to monitor the development of POT.

Simvastatin decreases hyperbaric oxygen-induced acute lung injury by upregulating eNOS.

Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase competitive inhibitors, not only lower blood cholesterol but also exert pleiotropic and beneficial effects in various diseases. However, the effects of statins on acute lung injury (ALI) induced by hyperbaric oxygen (HBO) have not been investigated. The present study is the first to investigate the effects of simvastatin in ALI induced by HBO in 8- to 9-wk-old C57BL/6 mice exposed to 0.23 MPa [=2.3 atmosphere absolute (ATA)] hyperoxia (≥95% O2) for 6 h. Mice were either given simvastatin (20 mg·kg·-1·day-1) in saline or a saline vehicle for 3 days before oxygen exposure. Lung tissue, serum, and bronchoalveolar lavage fluid (BALF) were collected for analysis of proapoptotic proteins, low-density lipoprotein cholesterol (LDL-C) levels, and lung inflammation. Simvastatin treatment significantly reduced lung permeability, serum LDL-C levels, tissue apoptosis, and inflammation. However, simvastatin treatment had no effect on antioxidant enzyme activity, nicotinamide adenine dinucleotide phosphate oxidase 4 (NADPH4) expression, and Akt phosphorylation levels. Furthermore, we investigated the role of endothelial nitric oxide synthase (eNOS) in simvastatin protection through inhibiting eNOS activity with NG-nitro-l-arginine methyl ester (l-NAME; 20 mg/kg). Results showed that the beneficial effects of simvastatin on ALI induced by HBO (antiinflammatory, antiapoptotic, lipid lowering, and reduction in lung permeability) were reversed. These results showed that simvastatin curbs HBO-induced lung edema, permeability, inflammation, and apoptosis via upregulating eNOS expression and that simvastatin could be an effective therapy to treat prolonged HBO exposure.

PDTC ameliorates decompression induced-lung injury caused by unsafe fast buoyancy ascent escape via inhibition of NF-κB pathway.

Nuclear factor kappa B (NF-κB) is the critical transcriptional factor in the pathogenesis of acute lung injury (ALI). NF-κB regulates the expression changes of inflammatory factors such as tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin 6 (IL-6). In a previous study we showed that decompression sickness (DCS) caused by simulated unsafe fast buoyancy ascent escape (FBAE) could result in ALI, which was characterized by expression changes of inflammatory factors in rat lung tissue. The purpose of the present work was to study the roles of NF-κB and TNF-α in the process of DCS-induced rat lung injury caused by simulated unsafe FBAE. The research methods aimed to detect the rat lung tissue messenger ribonucleic acid (mRNA) and protein level variations of NF-κB, inhibitory ×B (I×B), TNF-α, IL-1ß, IL-6, IL-10 and IL-13 by using pretreatment of the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) and TNF-α antibody (Ab). Our experimental results demonstrated that PDTC could improve the survival rate of the rats with DCS caused by unsafe FBAE more effectively than TNF-α Ab. However, the inhibition of TNF-α Ab on the nuclear translocated protein expression of NF-κB was more effective than PDTC. Both PDTC and TNF-α Ab can abrogate the increment of the rat lung tissue mRNA levels of TNF-α, IL-1ß, IL-6 and protein levels of NF-κB, TNF-α, IL-1ß effectively and increase the rat lung tissue content of I×B significantly. In conclusion, TNF-α-mediated NF-κB signaling may be one of the critical signaling pathways in the pathogenesis of DCS-induced rat lung injury caused by simulated unsafe FBAE. PDTC may ameliorate this type of injury partly through inhibiting the NF-κB pathway.

Expression changes of inflammatory factors in the rat lung of decompression sickness induced by fast buoyancy ascent escape.

Fast buoyancy ascent escape is one of the major naval submarine escape maneuvers. Decompression sickness (DCS) is the major bottleneck to increase the depth of fast buoyancy ascent escape. Rapid decompression induces the release of inflammatory mediators and results in tissue inflammation cascades and a protective anti-inflammatory response. In our previous study, we found that DCS caused by simulated fast buoyancy ascent escape could induce acute lung injury (ALI) and the expression changes of the proinflammatory cytokines: tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß and IL-6 in rat lung tissue. In order to study the expression change characteristics of TNF-α, IL-1ß, IL-6, IL-10 and IL-13 in the rat lung of DCS caused by simulated fast buoyancy ascent escape, we detected the rat lung mRNA and protein levels of TNF-α, IL-1ß, IL-6, IL-10 and IL-13 at 0.5 hour after DCS caused by simulated fast buoyancy ascent escape (fast escape group), compared with the normal control group (control group) and diving DCS (decompression group). We observed that DCS caused by simulated fast buoyancy ascent escape could increase the mRNA levels of TNF-α, IL-1ß, IL-6, IL-10, and the protein levels of TNF-α, IL-10 in rat lung tissue. At the same time, we found that the protein level of IL-13 was also downregulated in rat lung tissue. TNF-α, IL-10 and IL-13 may be involved in the process of the rat lung injury of DCS caused by simulated fast buoyancy ascent escape. In conclusion, the expression changes of inflammatory factors in the rat lung of DCS caused by simulated fast buoyancy ascent escape were probably different from that in the rat lung of diving DCS, which indicated that the pathological mechanism of DCS caused by simulated fast buoyancy ascent escape might be different from that of diving DCS.

Expression changes of TNF-α, IL-1ß and IL-6 in the rat lung of decompression sickness induced by fast buoyancy ascent escape.

Fast buoyancy ascent escape is the general submarine escape manner adopted by the majority of naval forces all over the world. However, if hyperbaric exposure time exceeds the time limit, fast buoyancy ascent escape has a high risk to result in decompression sickness (DCS). Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 have been all implicated in the process of inflammation associated with acute lung injury (ALI). Our work demonstrated that DCS caused by simulated fast buoyancy ascent escape could induce ALß in the rat model. The purpose of the present work was to study the expression changes of TNF-α, IL-1ß and IL-6 in the rat lung affected by DCS caused by simulated fast buoyancy ascent escape. The lung tissue mRNA levels of TNF-α, Il-1ß and Il-6 were significantly increased at 0.5 hour after DCS caused by simulated fast buoyancy ascent escape. The lung contents of TNF-α, IL-1ß and IL-6 were at an expression peak at 0.5 hour, although showing no statistical difference when compared with the normal control group. In conclusion, the rat lung expression variations of TNF-α, IL-1ß and IL-6 are the most obvious at 0.5 hour within 24 hours after the lung injury by DCS caused by simulated fast buoyancy ascent escape.

Protective role of peroxisome proliferator-activated receptor-ß/δ against pulmonary oxygen toxicity mediated through changes in NOS expression levels.

Recent studies have demonstrated that peroxisome proliferator-activated receptor-beta/delta (PPAR-ß/δ) has a protective effect during lung injury induced by bleomycin and polymicrobial sepsis, but its function in pulmonary oxygen toxicity is unknown. In this study, we used GW0742, a PPAR-ß/δ agonist, and GSK0660, a PPAR-ß/δ antagonist, to test the role of PPAR-ß/δ in lung injury due to hyperbaric oxygen (HBO2) exposure. Lung injury was induced in rats by HBO2 exposure (2.3 ATA, 100%O2, 8 hours). Sixty male Sprague-Dawley rats were randomly divided into 6 groups: air+vehicle, air+GW0742, air+GSK0660, HBO2+vehicle, HBO2+GW0742, and HBO2+GSK0660. Rats were injected with vehicle or GW0742 (0.3 mg/kg, i.p.) or GSK0660 (1 mg/kg, i.p.) at 1 hour, 6 hours, and 12 hours before either air or oxygen exposure. Administration of GW0742 to rats exposed to HBO2 significantly reduced the observed lung injury, extravascular lung water, total protein levels in bronchoalveolar lavage fluid, and the levels of iNOS and nNOS in the lungs when compared to untreated rats exposed to HBO2. Treatment of rats with GSK0660 exacerbated lung injury and elevated the levels of nNOS and eNOS in the lungs. In addition, nNOS and eNOS knock-out mice were examined. The results indicated that after HBO2 exposure, the lung injury was obviously decreased in the nNOS(-/-)+GSK0660 mice compared to the wild-type +GSK0660 mice; furthermore, administration of GSK0660 significantly elevated the lung injury in the eNOS(-/-) mice. Collectively, these data indicate that PPAR-ß/δ activation can protect against pulmonary oxygen toxicity in the lungs of rats through changes in the expression of NOS.

Effects of different simulated submarine escape depths by free ascent in animal models.

Objective: If a damaged submarine cannot be rescued in time, it is necessary to carry out a submarine escape by free ascent. Decompression illness is the greatest threat to the safety of submariners. The maximum depth at which a safe escape can be carried out is unknown. This study intends to explore the maximum safe escape depth by observing the effects of simulated submarine escape at different depths on animal models. Methods: We evaluated pulmonary function indexes, blood gas values, blood cell counts, the myocardial enzyme spectrum, coagulation parameters, and proinflammatory cytokine levels in rats, electrocardiographic activity in rabbits after simulated 150-m, 200-m, 220-m, and 250-m submarine escape by free ascent. Results: An escape depth of 150 m did not cause significant changes in the indicators. An escape depth of >200 m led to pulmonary ventilation and gas diffusion dysfunction, hypoxemia, myocardial ischemia, and activation of the fibrinolytic and inflammatory systems. The magnitudes of the changes in the indicators were proportional to escape depth. Conclusion: An escape depth of 150 m in animal models is safe, whereas escape at > 200 m can be harmful.

Lung function changes in divers after a single deep helium-oxygen dive.

INTRODUCTION: This study measured pulmonary function in divers after a single helium-oxygen (heliox) dive to 80, 100, or 120 metres of sea water (msw). METHODS: A total of 26 divers participated, of whom 15, five, and six performed a 80, 100, or 120 msw dive, respectively. While immersed, the divers breathed heliox and air, then oxygen during surface decompression in a hyperbaric chamber. Pulmonary function was measured twice before diving, 30 min after diving, and 24 h after diving. RESULTS: At 30 min after the 80 msw dive the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and the maximum expiratory flow at 25% of vital capacity (MEF25) values decreased (89.2% to 87.1% and 2.57 L·s⁻¹ to 2.35 L·s⁻¹, P = 0.04, P = 0.048 respectively) but FEV1/FVC returned to the baseline values by 24 h post-dive. Other pulmonary indicators exhibited downward trends at 30 min after the dive, but statistical significance was lacking. Interestingly, though several parameters decreased after the 100 msw dive, statistical significance was not reached. After the 120 msw dive, the FEV1/FVC and MEF75 decreased (90.4% to 85.6% and 8.05 L·s⁻¹ to 7.46 L·s⁻¹, P = 0.01, P = 0.007). The relatively small numbers of subjects who dived to 100 and 120 msw depths may explain the inconsistent results. The subjects diving to 100 and 120 msw were more trained / skilled, but this would not explain the inconsistencies in results between these depths. CONCLUSIONS: We conclude that single deep heliox dives cause a temporary decrease in FEV1/FEV and MEF25 or MEF75, but these changes can recover at 24 h after the dive.

Different activation of ERK1/2 and p38 with hyperbaric oxygen in dorsal root ganglion.

Prolonged hyperbaric oxygen exposure causes pulmonary and nervous system toxicity, although hyperbaric oxygen treatment has been used to treat a broad spectrum of ailments. In the current study, animals have been exposed to 100% oxygen at a pressure of 2.3 atmospheres absolute (ATA) for two, six and 10 hours or 0.23 MPa normoxic hyperbaric nitrogen (N2-O2 mixture, oxygen partial pressure = 21 kPa) for 10 hours. Then we investigated whether ERK1/2 and p38 had been activated in the dorsal root ganglion (DRG) by hyperbaric conditions. Using Western blot analysis, we found that the phosphorylation levels of ERK1/2 (phospho-ERK1/2) increased significantly (p < 0.05, n = 3 for each group) in the six-hour treatment of 100% oxygen at a pressure of 2.3 ATA. The phosphorylation levels of p38 (phospho-p38) increased significantly (p < 0.05, n = 3 for each group) in the 10-hour treatment of 100% oxygen at a pressure of 2.3 ATA--which was consistent with time course changes of an apoptosis marker, cleavage caspase-3--while the phospho-p38 decreased in the 10 hours of N2-O2 mixture. These results demonstrate that the ERK1/2 and p38 have been differently activated in the DRG by prolonged hyperbaric oxygen exposure.

Human Physiological Responses to a Single Deep Helium-Oxygen Diving.

Objective: The objective of this study was to explore whether a single deep helium-oxygen (heliox) dive affects physiological function. Methods: A total of 40 male divers performed an open-water heliox dive to 80 m of seawater (msw). The total diving time was 280 min, and the breathing helium-oxygen time was 20 min. Before and after the dive, blood and saliva samples were collected, and blood cell counts, cardiac damage, oxidative stress, vascular endothelial activation, and hormonal biomarkers were assayed. Results: An 80 msw heliox dive induced a significant increase in the percentage of granulocytes (GR %), whereas the percentage of lymphocytes (LYM %), percentage of intermediate cells (MID %), red blood cell number (RBC), hematocrit (hCT), and platelets (PLT) decreased. During the dive, concentrations of creatine kinase (CK), a myocardial-specific isoenzyme of creatine kinase (CK-MB) in serum and amylase alpha 1 (AMY1), and testosterone levels in saliva increased, in contrast, IgA levels in saliva decreased. Diving caused a significant increase in serum glutathione (GSH) levels and reduced vascular cell adhesion molecule-1 (VCAM-1) levels but had no effect on malondialdehyde (MDA) and endothelin-1 (ET-1) levels. Conclusion: A single 80 msw heliox dive activates the endothelium, causes skeletal-muscle damage, and induces oxidative stress and physiological stress responses, as reflected in changes in biomarker concentrations.

[Effect of nuclear radiation on rat model of decompression sickness induced by large depth rapid floating escape].

Objective: To investigate the effects of different doses of nuclei exposure at different time on morbidity, mortality, and damage indicators in a rat model of decompression sickness caused by rapid flotation escape at a large depth. Methods: Eighty male SD rats were randomly divided into blank control group, escape control group and six intervention groups (escape at 4 hours after 4 Gy radiation, escape at 4 hours after 6 Gy radiation, escape at 4 hours after 12 Gy radiation, escape at 8 hours after 4 Gy radiation, escape at 8 hours after 6 Gy radiation, escape at 8 hours after 12 Gy radiation). Rats in intervention groups were exposed to different doses of γ-ray (4,6,12 Gy, respectively), and then were carried out a large depth and rapid buoyancy escape experiment (maximum pressure depth of 150 m). The changes of lung W/D, spleen index and plasma IL-1ß levels were analyzed. Results: Compared with the blank control group, decompression sickness incidence and mortality of rats in escape groups after nuclear exposure were increased significantly. In 4 Gy and 6 Gy irradiation groups, higher morbidity and mortality were observed in rats which escaped at 4 h post nuclear exposure when compared with rats in 8 h groups. Consistent with the changes in morbidity and mortality, the wet / dry ratio of lung tissue, the pathological damage of lung tissue, and the decrease of spleen index showed the same trends: the changes were obvious at 4 h after lower doses nuclear radiation (4 Gy and 6 Gy), not at 8 h. However, these indicators all changed markedly at 4 and 8 h after higher doses nuclear radiation (12 Gy). Plasma IL-1ß levels were significantly increased in each post-radiation exposure group when compared with the blank control group and the exposed control group. Conclusion: Nuclear radiation-induced lung injury, the damaged immune function and elevated plasma inflammatory factor concentrations increase the risk of decompression sickness after rapid ascent.

[Edaravone has a protective role in a mouse model of pulmonary oxygen toxicity].

OBJECTIVE: To find if edaravone can play a protective role in a mouse model of pulmonary oxygen toxicity and explore the intervention mechanism. METHODS: Thirty male C57BL/6 mice were randomly divided into 3 groups(Air +Vehicle, Hyperbaric oxygen(HBO) +Vehicle and HBO + Edaravone). Mice were either given edaravone (5 mg/(kg·d)) in sterilized water or a sterilized water vehicle for 3 days before oxygen exposure. Mice in HBO groups were exposed to 0.23 MPa hyperoxia (≥95% O2) for 6 h. Lung tissues were collected and the wet/dry ratio of lung were analyzed. For histologic analysis, lung sections were stained with hematoxylin and eosin (HE). Proinflammatory cytokine levels and antioxidant enzyme activities in lungs were determined by using ELISA kits. The expression levels of pro-apoptosis protein were determined with Western blot analysis. RESULTS: Edaravone treatment could significantly reduce lung permeability, decrease tissue pro-apoptosis protein (cleaved-caspase3) and inflammation (IL-1ß). However, edaravone treatment had no effect on antioxidant enzyme activities. CONCLUSION: These results showed that edaravone treatment had a protective role in pulmonary oxygen toxicity through curbing inflammation and apoptosis.

[Effect of different pressure oxygen pre-breathe in diving decompression sickness of rats].

OBJECTIVE: To investigate the effect of different pressure oxygen pre-breathing in preventing decompression sickness of rats. METHODS: Forty male SD rats were randomly divided into 4 groups: decompression sickness (DCS) group and three oxygen pre-breathing groups with 1 ATA, 2 ATA and 3 ATA pressure respectively. The rats of DCS group were placed in the hyperbaric chamber and the chamber was compressed evenly within 3 minutes to depths of 7 absolute atmosphere(ATA) and held at the designated depth for 60 min, then decompressed (3 min) at constant speed to the surface pressure. After that, the rats were taken out for further detection. While the rats of oxygen pretreatment groups pre-breathed different pressure oxygen for 20 min before entering into chamber. The mortality and behavioral of rats were observed with 30 min post decompression. The dry/wet ratio of the lung, protein levels in the bronchoalveolar lavage fluid (BALF), and the inflammatory cytokine tumor necrosis factor (TNF-alpha) expression were also tested. RESULTS: Compared with that of the DCS group, the mortality and morbidity of oxygen pre-breathe groups didn't change obviously. But the total BALF protein level and the inflammatory cytokine TNF-alpha expression of 1 ATA oxygen pre-breathe group were obviously decreased, while the dry/wet ratio of lung as obviously increased instead (P < 0.05). CONCLUSION: Although preoxygenation can' t obviously change the mortality and mobidity of rats, normal pressure oxygen pre-breathing can mitigate the protein infiltration in BALF and the expression of inflammatory cytokine in lung tissue.

Inducible Costimulator Gene-Transduced Bone Marrow-Derived Mesenchymal Stem Cells Attenuate the Severity of Acute Graft-Versus-Host Disease in Mouse Models.

In murine allogeneic transplantation models, ICOS gene-transduced bone marrow-derived mesenchymal stem cells (MSCs(ICOS-EGFP)) were evaluated for their effects on GvHD severity and long-term survival. Lethally irradiated BALB/c or first filial generation of BALB/c and C57BL/6 (CB6F1) mice were transplanted with bone marrow cells and splenocytes from C57BL/6 mice to establish acute GvHD models. Recipient mice were injected with MSCs(ICOS-EGFP), MSCs, MSCs(EGFP), ICOS-Ig fusion protein, MSCs + ICOS-Ig, or PBS (control group). Long-term survival, GvHD rates and severity, CD4(+) T-cell apoptosis and proliferation, and Th1/Th2/Th17 effecter cell polarization were evaluated. In the C57BL/6 → CB6F1 HSCT model, the long-term survival in the MSC(ICOS-EGFP) group was higher than that in the GvHD group (74.29 ± 7.39% vs. 0, p < 0.01), and this survival rate was also higher than that in the MSC, ICOS-Ig, or MSC + ICOS-Ig groups (42.86 ± 8.36%, p = 0.004; 48.57 ± 8.45%, p = 0.03; or 50.43 ± 8.45% p = 0.04, respectively). The survival advantages of MSC(ICOS-EGFP)-treated group were confirmed in the C57BL/6 → BALB/c HSCT model. In both HSCT models, the low mortality in the MSC(ICOS-EGFP) group was associated with lower incidence and severity of acute GvHD. Treatment with MSCs(ICOS-EGFP) induced more CD4(+) T-cell apoptosis compared with that in the GvHD group. The effect on CD4(+) T cells was shown as early as day 2 and maintained until day 14 (p < 0.05 on days 2, 3, 7, and 14). Furthermore, we demonstrated that MSCs(ICOS-EGFP) were able to suppress Th1 and Th17 polarization and promote Th2 polarization on both protein expression and gene transcription levels. Higher serum levels of IL-4, IL-10, and lower levels of IFN-γ, IL-2, IL-12, and IL-17A were detected in the MSC(ICOS-EGFP) group. The MSCs(ICOS-EGFP) could also induce GATA-3, STAT6 expression and inhibit T-bet, STAT4, ROR-γt expression. Our results showed that injection of MSCs(ICOS-EGFP) is a promising strategy for acute GvHD prevention and treatment. It provides synergistic benefits of MSC immune modulation and ICOS-B7h pathway blockage.

Clopidogrel reduces the inflammatory response of lung in a rat model of decompression sickness.

Inflammation and platelet activation are critical phenomena in the setting of decompression sickness. Clopidogrel (Clo) inhibits platelet activation and may also reduce inflammation. The goal of this study was to investigate if Clo had a protective role in decompression sickness (DCS) through anti-inflammation way. Male Sprague-Dawley rats (n=111) were assigned to three groups: control+vehicle group, DCS+vehicle, DCS+Clo group. The experimental group received 50 mg/kg of Clo or vehicle for 3 days, then compressed to 1,600 kPa (150 msw) in 28 s, maintained at 150 msw for 242 s and decompressed to surface at 3m/s. In a control experiment, rats were also treated with vehicle for 3 days and maintained at atmospheric pressure for an equivalent period of time. Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine detection. The pathology and the wet/dry ratio of lung tissues, immunohistochemical detection of lung tissue CD41 expression, the numbers of P-selectin positive platelets and platelet-leukocyte conjugates in blood were tested. We found that Clo significantly reduced the DCS mortality risk (mortality rate: 11/45 with Clo vs. 28/46 in the untreated group, P<0.01). Clo reduced the lung injury, the wet/dry ratio of lung, the accumulation of platelet and leukocyte in lung, the fall in platelet count, the WBC count, the numbers of activated platelets and platelet-leukocyte complexes in peripheral blood. It was concluded that Clo can play a protective role in decompression sickness through reducing post-decompression platelet activation and inflammatory process.

Protective role of peroxisome proliferator-activated receptor ß/δ in acute lung injury induced by prolonged hyperbaric hyperoxia in rats.

Peroxisome proliferator-activated receptor (PPAR)-ß/δ is a transcription factor that belongs to the PPAR family, but the role of PPAR-ß/δ in acute lung injury (ALI) induced by hyperbaric oxygen is unknown. In this study we investigated if PPAR-ß/δ activation protects from hyperoxia-induced ALI in a rat model. ALI was induced by prolonged hyperbaric oxygen (HBO2) (2.3ATA, 100% O2) for 8h. Administration of PPAR-ß/δ agonist GW0742 (0.3mg/kg, i.p.) at 1 and 6h prior to HBO2 exposure significantly reduced the (1) lung injury, (2) proinflammatory cytokines (TNF-α, IL-1ß, IL-6), (3) apoptosis (Bax/Bcl-2, cleaved-caspase-3 and TUNEL), (4) nuclear factor (NF)-κB expression level and DNA binding activity in the nucleus, and (5) extracellular signal-regulated kinase (ERK)1/2 phosphorylation and markedly elevated (6) superoxide dismutase and glutathione peroxidase activities as well as (7) IκB expression. However, administration of the PPAR-ß/δ antagonist GSK0660 abolished these protective effects. These findings indicate that activation of PPAR-ß/δ ameliorates hyperoxia-induced ALI in rats by up-regulating antioxidant enzyme activity as well as suppressing inflammation and apoptosis.

[The change of NOS in pulmonary oxygen toxicity induced by different oxygen pressure].

OBJECTIVE: Long time exhaled oxygen will induced oxygen toxicity. Some studies had found that different pathology may exised in normobaric and hyperbaric pulmonary oxygen toxicity, and nitric oxide synthase (NOS) may play a role. In this study, we discussed the change of NOS in normobaric and hyperbaric pulmonary oxygen toxicity. METHODS: Sixty male SD rats were randomly divided into 6 groups (n = 10), exposed to 1 ATA (atmosphere absolute), 1.5 ATA, 2 ATA, 2.5 ATA and 3 ATA, 100% oxygen for 56, 20, 10, 8, 6 hours respectively. Rats were exposed to air as control. After exposure, the protein in bronchoalveolar lavage fluid (BALF), the wet/dry weight of lung and the expression of eNOS, nNOS in lung were defined. RESULTS: As compared to air group, the protein in BALF, the wet/dry of lung were significantly elevated in 1.0 ATA group, while these changes were not so obviously in the other groups, and these changes in hyperbaric oxygen group (approximately 1.0 ATA) were significantly decreased as compared with nonnrmobaric oxygen group (1.0 ATA). The expression of nNOS were not changed in normobaric and hyperbaric pulmonary oxygen toxicity, while the expression of eNOS was significantly decreased in 2 ATA group, and significantly elevated in 2.5 ATA and 3 ATA group. CONCLUSION: The expression of eNOS can change when exposed to different pressures of oxygen.

[Change of adhesion molecules in the lungs of rat with decompression sickness].

OBJECTIVE: To investigate the change of adhesion molecules in the lungs of rats suffered with decompression sickness (DCS). METHODS: Male SD rats were placed in the hyperbaric chamber, the chamber was compressed within 3 minutes to depths of 7 absolute atmosphere (ATA) and held at the designated depth for 60 min, then rapidly decompressed (3 min) to the surface. Rats were observed for signs of DCS after decompression. The brains, hepatis, and lungs were removed at 30 min, 6 h, 24 h post decompression, fixed and stained with hematoxylin eosin for routine histologic analysis. Lung paraffin sections were immunostained for the expression of intercellular adhesion molecule-1 (ICAM-1), E-selectin and major histocompatibility complex class II molecule (MHC-II). 2% evans blue dye in normal saline was injected 30 minutes prior to 6 h, 24 h before decompression. After 30 min, animals were perfused with 0.9% normal saline and lungs were harvested. Evans blue in the plasma was quantified by wavelength spectrophotometric analysis at 620 nm. RESULTS: Results showed that there were hemorrhage and edema changes in the lungs, liver and brain at 30 min post decompression. Compared with control animals maintained at 1 ATA, the levels of E-selectin, ICAM-1 and MHC-II in the lungs of DCS rats were significantly increased post decompression. Compared with control animals, evans blue in the plasma was much higher at 6 h, 24 h post decompression. CONCLUSION: The bubble-induced adhesion molecule-mediated endothelial activation may be involved in the pathogenesis of DCS.

[Changes of adhesion molecules and adenosine in divers post 480 heliox saturation diving].

OBJECTIVE: To investigate the changes of adhesion molecules, cyclic adenosine monophosphate(cAMP) and cyclic guanosine monophosphate (cGMP) in divers post 480 heliox saturation diving. METHODS: Four divers were compressed within 96 hours to depths of 480 m with heliox-oxygen and held at the designated depth for 49 hours, excursion to 493 m during their saturation stay, then decompressed within 302 hours to the surface. The blood samples were collected before compression and post decompression, the expression level of intercellular adhesion molecule-1(ICAM-1), E-selectin, P-selectin, cAMP, cGMP were detected with ELISA analysis box. RESULTS: Compared with the levels of CAMs before compression, the levels of ICAM-1, E-selectin, P-selectin and cGMP in the serum were changed post decompression (P > 0.05). The levels of cAMP were significantly elevated post decompression (629.91 +/- 75.01) nmol/L vs (66.72 +/- 83.15) (P < 0.05). CONCLUSION: The decompression schedule in this heliox saturation diving is safe, the decompression sickness pathology in this diving has not been induced. But the stress response of divers are enhanced by this great depth saturation diving.

[The variation of PPAR pathway molecules in the lung tissue of rats under hyperbaric oxygen exposure].

OBJECTIVE: To study the expression pattern of peroxisome proliferator-activated receptor (PPAR) pathway molecules in rat lung tissue under hyperbaric oxygen exposure. METHODS: Twenty seven male SD rats were randomly divided into hyperbaric normoxia group (0.23 MPa air), hyperbaric oxygen treatment time series group (0.23 MPa oxygen, were exposed for 2 h, 4 h, 6 h or 8 h), continuous small flow of ventilation to maintain cabin O2 concentration > 99%. HE staining of lung tissue morphological changes and application oligo microarray to each time point lung were observed. Part of the PPAR pathway genes were validated by RT-PCR. RESULTS: Compared with hyperbaric normoxia group, the lung injury caused by hyperbaric oxygen treatment gradually deteriorated during the time series. Expression microarray analysis of gene ontology (Go) enrichment analysis results in a class of PPAR pathway class included multiple PPAR pathway molecule. RT-PCR results suggested that PPAR-8 and PPAR-Y were up-regulated in the lung tissue after a long time exposure to hyperbaric oxygen. CONCLUSION: Pro-longed hyperbaric oxygen exposure causing pulmonary oxygen toxicity can induce the activation of the PPAR pathway.