Effect Of Macrophage Inflammatory Protein 2 On Pulmonary Oxygen Toxicity

Hyperbaric oxygen exposure involves in diving medicine work and clinical hyperbaric oxygen treatment. The application of high partial pressure oxygen can improve the inert gas desaturation velocity when reducing pressure, shorten the time of reducing pressure, improve underwater operation efficency . and there is clear treatment result to some hypoxia diseases. But inhaling high partial pressure oxygen for a long time bring the issue of oxygen toxicity. Oxygen toxicity is classified as eye type . brain type, and pulmonary type. Pulmonary oxygen toxicity is mainly showed as coughing, dyspnea. Pathology observations show that main changes in forepart time are the lung congestion in large area, hemorrhage and hydroncus. inflammation cell infiltration. PMN in especial. PMN's assembling and activation can injury vessel endothelial cell and perivascular tissue.which mostly accouts for the inflammation injury and MODS .Macrophage inflammation protein - 2 (MIP-2) is the primary chemokine in mouse lung. The methods of Pathology, Immunohistochemistry. Molecular biology are used to verify the correlation between MIP-2 and lung injury. The research aims to discuss the mechanism of inflammation injury in pulmonary oxygen toxicity,and provide new experiment data for the cause of pulmonary oxygen toxicity,and find new treatment strategy.The C57BL/6 mouse breathe pure oxygen in closed cabin for different coursesto duplicate pulmonary oxygen toxicity model.which is guided by Wright's concept of UPTD(unit pulmonary toxic dose). The animals are divided into six groups which are named as control group .650UPTD group, 850UPTD group. 1100UPTD group, antibody group . norm oxygen group(hyperbaric and normal 0: density group).Every group includes eight mouses. The major objectives of this study are:l duplicating the mouse model of pulmonary oxygen toxicity; 2 observing the pathologic changes of mouse lung tissue after pulmonary oxygen toxicity; 3 observing the myeloperoxidse changes of mouse lung tissue after pulmonary oxygen toxicity;4 with histological pathology and MPO changes, exploring changes of MIP-2mRNA and M1P-2 after pulmonary oxygen toxicity. This study was to explore the function of MIP-2 in inflammation cause after hyperbaric oxygen exposure, and use MIP-2 antibody to neutralize MIP-2. aiming to perfect the mechanism of pulmonary oxygen toxicity and provide experimental basis for the reasonable utilization of oxygen and new treatment methods of pulmonary oxygen toxicity. The main results of our study are as follows:1.Using the healthy mice, we carried out different schemas of hyperbaric oxygen exposure . After breathing 3ATA pure oxygen for different time, then being decompressed at safe program, none of the mouse was of palsy, shivered or died; 650UPTD.850UPTD, 1100UPTD group have less activities . tachypnea. But the others are normal. The results suggested the mouse model of pulmonary oxygen toxicity has been established.2.Pathologic observations: pulmonary collapse, hemorrhage, congestion andleucocyte assembling in lung interstitial are found in 850UPTD group,llOOUPTD group; alveoli dilatation, bronchus excretion's elevation, alveolar epithelium abscission are observed clearly in 1100UPTD group. PMN infiltration is not clear in control group, 650UPTD group, antibody group . norm oxygen group.3.In contrast with control group, the expression of MIP-2 in mouse lung tissue of 850UPTD,llOOUPTD group is increased(/?<0.05) , As is shown in IHC sections,MIP-2 are both expressed in tracheal epithelium and alveolar epithelium, tracheal epithelium in especial.MIP-2 expression in cytoplasm is prior to MIP-2 expression in nucleus.4.The transcriptional levels of MIP-2 mRNA in lung tissue after hyperbaric oxygen exposure are detected by RT-PCR assay. The levels of MIP-2 mRNA of 650UPTD group .850UPTD and llOOUPTD group are markedly higher than that of control group(p<0.05); The level of MIP-2 mRNA of normal oxygen group is not obviously higher than that of control group, suggesting the hyperbaric effect can be excluded; The level of MIP-2 mRNA of antibody group is obviously lower than that of 850UPTD group(/?<0.01). suggesting the antibody plays an important role in decreasing MIP-2 in lung tissue.5.The MPO assay is used to show PMN sequestration and activation in lung tissue of pulmonary oxygen toxicity mouse. The MPO activity of normal group and 650UPTD group is not obvious higher than control group(p>0.05); The MPO activity of 1100UPTD group and 850UPTD group is higher than that of control group(p<0.01). The MPO activity of antibody group is lower than that of 850UPTD group(/?<0.01).