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The Mechanism And Pharmacological Prevention Of Acute Lung Injury Induced By Inhalation Of Liquid Rocket Propellant

Posted on:2005-05-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:S LiuFull Text:PDF
GTID:1104360122992032Subject:Respiratory medicine
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Unsymmetrical dimethylhydrazine (1,1-dimethylhydrazine, UDMH) and dinitrogen tetroxide (N2O4) are highly volatile and reactive compounds used primarily as a liquid rocket propellant. Acute inhalation of UDMH and N2O4 is described with particular attention to the development of pulmonary edema as a harbinger of more severe the other system toxicity. Some clinical observation were documented that the patients who inhaled the toxic vapor manifested the acute respiratory embarrassment, which fit in with the diagnostic criteria of acute lung injury (ALI), even acute respiratory distress syndrome (ARDS). However the mechanism of the ALI/ARDS induced by the inhalation has been not clear, and few drugs can be applied to the treatment. In this experiment, the rat model of ALI was established by inhalation of UDMH and N2O4. Then the imbalance of oxidation andanti-oxidation, the role of pulmonary surfactant (PS) and polymorphonuclear leukocyte (PMN) in the ALI were investigated. Thereafter the pharmacological prevention of the ALI was carried out with W-acetylcysteine (NAC), radix salviae miliorrhizae (RSM) and methylprednisolone (MP).Methods: 1) Experimental rats inhaled UDMH 400ppm for ten minutes and N2O4 50ppm for ten minutes. After the inhalation, these rats were killed on the time of 2, 6, 12, 24, 48 hour, named the corresponding group respectively. Additional rats were as control group. The wet to dry ratio (W/D) of lung tissue, total protein and lactate dehydrogenase (LDH) of bronchoalveolar lavage fluid (BALF) were measured. General manifestation and histopathology were observed. 2) The superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) of lung tissue, and the MDA of plasma were measured in above these rats. 3) The surface tension (gamma) and minimal surface tension (ymin) of BALF, the content of phosphatidyloholine (PC) and phosphatidyl ethanolamine (PE) of BALF were measured in above these rats. 4) The myeloperoxidase (MPO) of lung tissue, and the positive express CD lib/CD 18 of PMN were measured in above these rats. Another rats were made neutropenia with pretreated intravenous nitrogen mustard, and the index of lung injury were observed in these neutropenic rats after inhaling the UDMH and N2O4. 5) NAC was treated after the inhalation immediately to investigate the preventive effect for the ALI. The index of lung injury, the activity of SOD and GSH-Px of lung tissue were measured in these rats. 6) RSM was treated after the inhalation immediately to investigate the preventive effect for the ALI. Theindex of lung injury, the activity of SOD and GSH-Px of lung tissue were measured in these rats. 7) MP was treated after the inhalation immediately to investigate the preventive effect for the ALL The index of lung injury, the activity of SOD and GSH-Px of lung tissue, the MDA of plasma, the y, ymin, PC, PE of BALF were measured in these rats.Results: 1) These rats who inhaled the UDMH and N2O4 showed tachypnea and respiratory distress, especially from 6 to 16 hour after the inhalation. The W/D of lung tissue, total protein and LDH of BALF increased in the groups of 2h, 6h, 12h, while these values restored in the group of 24h and 48h. Histopathology of these rats showed severe interstitial pulmonary edema and exudation in alveolar cavity. 2) The activity of SOD and GSH-Px of lung tissue decreased in the groups of 2h, 6h, 12h (P<0.05), and the activity restored in the group of 24h or 48h. The MDA of plasma increased in the groups of 12h and 24h. The W/D of lung tissue correlated with the activity of SOD and GSH-Px of lung tissue respectively (P<0.01). 3) The y of BALF increased in all groups of post-inhalation (P<0.05), and the ymin increased in groups of 2h, 6h, 12h, and 24h (P<0.05). The PC's content of BALF decreased in the group of 24h (P<0.05), and the opposite change occurred in the PE's content of BALF (P<0.05). The total protein of BALF correlated with the y and ymin of BALF respectively (P<0.01). 4) The activity of MPO of lung tissue didn't change statistically in all gr...
Keywords/Search Tags:Unsymmetrical dimethylhydrazine(UDMH), Dinitrogen tetroxide (N2O4), Acute lung injury(ALI), Peroxidation, Pulmonary surfactant(PS), Polymorphonuclear leukocyte (PMN), N-acetylcysteine (NAC), Radix salviae miliorrhizae (RSM), Methylprednisolone(MP)
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