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The HAPE Animal Model Establishment And The Its Mechanism Studies

Posted on:2010-10-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ChenFull Text:PDF
GTID:1114360278476784Subject:High Altitude Medicine
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In 1980's Chen's study showed that the large crystal solution infused could not only led to the increase of moisture capacity in lung, but also the increase of moisture capacity in hydrothorax, hydroperitoneum,liver and muscle. When 30% fluids of the bod weight was infused, the moisture capacity in lung was notable increase, However, the increase of moisture capacity in lung was not obvious and the signs of right congestive heart failure was come out, therefore, the increase of moisture capacity in liver was obvious. The moisture capacity in lung in 4500 m height was more than that in 6500 m height under the conditioning of anoxia. Liu's data showed that the pulmonary interstitial edema was successfully constructed by simulating the 5000 m height, and the number of pulmonary alveolar edema mainly happened within 48 hours was small and the degree was slight. Liu's study observed the change of moisture capacity in lung by simulating the 6000m height with mice and rats. The results showed that the moisture capacity in lung decreased in the first day, and the content increased in the second and third day, then the content gradually decreased from the forth to the seventh day, the difference was statistical significant than that of the control group by the simple anoxia. In 90's Luo constructed the HAPE model of rabit by the prevention of dexamethasone and nifedipine, however, the mechanism of HAPE mediated by the increase of permeability and pulmonary hypertension was recognized, the blocking of absorptive function was not further to study. In this study, the change of interstitial HAPE into alveolus HAPE by the control of physiological saline infused. The expression of AQP was regulated by dexamethason and propranolol dinitrate to interfere the absorptive function in order to duplicate the animal model of alveolus HAPE.1. The change of AQP5 and PAP in the condition of simulation height MethodThe pulmonary arterial pressure was examined by cardiac catheterization and AQP5 was detectd by western-blot and immunohistochemisty and pathological section in rats undergone anoxia combined with cold and movement under the condition of simulation 4000 m height.Results1 The pulmonary arterial pressure increase with the increase of time, the value was much higher in 72 h than that in 48h; the increase of AQP5 was much higher in each experimental group than that in normal control group and the expression of AQP5 increased with time, the peak time of AQP5 expression was in 48 h, the expression was lower in 72 h than in 48 h.2 The PAP obviously increased under the conditioning of anoxia, anoxia combined with cold and anoxia combined with cold and movement than that the normal control group. There was not any change of pulmonary arterial pressure. The expression of AQP5 was lower in C group than that in N group and was higher in H group and HC group and HCE group than that in N group and decrease than that in the single anoxia group.ConclusionThe expression of AQP5 increased under the condition of anoxia, anoxia combined with cold and anoxia combined with cold and movement. The change of AQP5 was consisten with the moisture capacity in lung and the development of HAPE, which showed that AQP5 was very important in the development of HAPE.2. the construction of animal model of HAPE in rabbitMethodsThe body fluids of pulmonary circulation in rabbit was increase by transfusion, then the body fluids got into the interstitial tissue. The model of HAPE was be construct when the pulmonary alveolar edema reached over the peak.Results1. The increase of moisture capacity in lung was more in G group thant that in the control group at the 3700 m height, however, it was much less in the P group and D group than that in the control group, the difference was statistical significance.2 Three rabbits developed into HAPE in G group, two rabbits in the P group and no rabbits in the N group and D group.ConclusionThe aimal model of HAPE was successfully constructed by transfusion by drugs blocked reabsorption of lung and sleep interference under the conditioning of highland. 3.The study on the change of PAP and moisture capacity in lung in the simulation height of 5400 m in rabbitMethodsAll experience was divided into diferent groups. The N group: control group, no any intervention was performed. The PJ group received 15ml alcohol every time once a day.The PD group received intravenous dexamethasone (2mg/kg once a day). The PG group suffered from sleep interference by the light and three times acoustic stimulation in the whole nighttime. The PH group received continuing decompression in 5400 m height and the temperature was 14℃from 8:00 to 20:00 and 4℃from 20:00 to 8:00 at the next day, the humidity is the same to the environment. There was not any limitation in the food and drink. The pulmonary arterial pressure and ventricular pressure was detected on the first, the second, the third, the forth, the fifth and the seventh day, then the rabbit was kill and the lung was took out after the carotid arteries blood was drawed-out. Eight rabbits at least was used in each group.Results1 The increase of pulmonary arterial pressure was more in PJ group than that of P group, however, It is lower in PG group than that of P group. The difference was not statistical significance when the experimental groups were compared with the control group, respectively.2 The increase of moisture capacity in lung was more in the experimental groups than that of the control group. It was statistical significance between PS group and PG group and the increase was more in PS group. It was statistical significance between PJ group and PD group.3 The pulmonary arterial pressure gradually decreased in the group of depressure at 5400m, then the pulmonary arterial pressure gradually increased in the third day and began to decrease at the fifth day,4 The moisture capacity in lung obviously increased from the first day to the third day, the slightly decrease was seen from the third day to the forth day, then began to increase.Conclusion1 The moisture capacity in lung was significantly effected by infuse and sleep interference. The development of HAPE could be made by infuse and sleep interference. 2 The rabbits itself could regulated pulmonary arterial pressure and moisture capacity in lung under the conditioning of stress in the simulated 5400 m.4.The acute high altitude reaction and the change of PAP and moisture capacity in lung in rabbit at the height of 5374 m.MethodsThe death of rabbits at the height of 5374 m was detected from December to March of the next year.The pulmonary arterial pressure was examined by cardiac catheterization. The moisture capacity in lung was detected and pathological section was carried out to detect the pathology.ResultsThe more serious high altitude reaction and even death was detectd when the rabbits were took to the height of 5374 m. During the first 10 days, the number of death was small on the first 4 days and the peak time was reached from the fifth day to the seventh day, then the number of death decreased from the eighth day to the tenth day.2 The pulmonary arterial pressure obviously increased from the first two day to the third day, there was high statistical significance. The increase was not obvious from the forth day to the sixth day.3 The moisture capacity in lung gradually decreased when the rabbit reached the 5374 m height, then began to increase and the volume is much higher than that at the beginning time.4 The increase of moisture capacity in lung was more in transfusion group than that in the control group, however, The increase of moisture capacity in lung was obviously lower in the hexadecadrol group than that in the transfusion group. The increase was more in the s group than that in the D group, the difference was statistical significance. There was no statistical significance between control group and J and G group.Conclusion1 The high altitude reaction was more serious in the conditioning of cold, radiation, force of wind and change of temperature day and nigh on highland than that in the conditioning of depressure in hypobaric chamber on plains.2 The change of pulmonary arterial pressure at the 5400 m height showed that the increase of pulmonary arterial pressure was the main mechanism of pneumonedema. 3 The hexadecadrol obviously decreased the moisture capacity in lung at at the 5400 m height, which could be used to prevent the development of pneumonedema. The development of pneumonedema could be achieved by transfusion.5.The research of the rabbit WBC and clinical thereapy of the HAPEMethodsThe N group: control group, no any intervention was performed. The PH group received continuing decompression in 5400 m height and the temperature was 14℃from 8:00 to 20:00 and 4℃from 20:00 to 8:00 at the next day, the humidity is the same to the environment. There was not any limitation in the food and drink. The WBC of the hemo-rule was detected on the first, the second, the third, the forth, the fifth and the seventh day, Eight rabbits at least was used in each group. The WBC of rabbits at the height of 5374 m was detected.Results1 The increase of WBC was more in GQ group than that of N group, however, It is lower after 4 days in the simulated 5400 m. The difference was significantly when the experimental groups were compared with the control group, respectively.2 The increase was increased after 3 days at the height of 5374 m. The WBC of the 4d and 5d was significantly diference,but there is no statistical significance in 3 days.3. positive anti-inflammatory therapy group need shorter time ,there is significant diference between PITG and NITG .Conclusion1.The WBC of the hemo-rule examin is significantly increase,by simulate high altitude circumstance.2 The PITG's time may significantly decreased , and stronger cure effection.Conclusions of the papersThe change of pathophysiology and incidence was observed in rats at different time point under the conditioning of anoxia, cold and movement which was stimulated the environment of highland according to the characters of HAPE in clinic. At the same time, The effect of transfusion, sleep interference, alcohol and hexadecadrol in rabbits on the pulmonary arterial pressure and moisture capacity in lung was observed and the change of pathophysiology was explored under the conditioning of the 5400m height of stimulation and the real 5374m height. Our study showed that the most effected factor on the moisture capacity in lung was transfusion and sleep interference. It is not the same on the effect of real height and the combination of depressure with anoxia at the plains on moisture capacity in lung and the expression of PAP. Then the rabbits brought from the plains received transfusion in the phase acute high altitude reaction in the real highland in the research center of altitude disease in the General Hospital, Military district of Tibet at 3700 m height, and the drugs blocked reabsorption of lung and sleep interference was used to induce the pulmonary alveolar edema. The model of HAPE was successfully constructed.The main conclusion:1 The expression of AQP5 increased under the condition of anoxia, anoxia combined with cold and anoxia combined with cold and movement. The change of AQP5 was consisten with the moisture capacity in lung and the development of HAPE, which showed that AQP5 was very important in the development of HAPE.2 The change of pulmonary arterial pressure at the 5400 m height showed that the increase of pulmonary arterial pressure was the main mechanism of pneumonedema.3 The high altitude reaction was more serious in the conditioning of cold, radiation, force of wind and change of temperature day and nigh on highland than that in the conditioning of depressure in hypobaric chamber on plains.4 The hexadecadrol obviously decreased the moisture capacity in lung at at the 5400 m height, which could be used to prevent the development of pneumonedema.5 The moisture capacity in lung was significantly effected by infuse and sleep interference. The development of HAPE could be made by infuse and sleep interference.6 The aimal model of HAPE was successfully constructed by transfusion and the drugs blocked reabsorption of lung and sleep interference under the conditioning of highland.7. The PITG may significantly decreased cured time,and cure effections was more stronger..
Keywords/Search Tags:high altitude pulmonary edema(HAPE), pulmonary arterial pressure (PAP), initiative reabsorption disord, aquaporins5(AQP5), pulmonary water contain (PWC), pathogenesis, animal model
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