Mechanisms Of High Altitude Hypoxia And Ibuprofen Intervention On Cytokines In Rats

Persons who are not acclimatized and ascend rapidly to high altitudes will appear symptoms of discomfort, such as nausea, vomiting, fatigue and so on. Some of them may have severe acute high-altitude illness, if they are not treated early, they may be death. However, the pathogenesis of acute mountain sickness is still unknown. The development of high altitude drugs are slowly. People’s lives and health are threatened by the high altitude diseases. Therefore, exploring the mechanisms of acute high-altitude illness and developing the anti-hypoxia protective drugs are very important. We will generate acute high-altitude exposure rat models and study the effects of hypoxia on cytokines in rats. To study the protective roles of ibuprofen against hypoxia injury, the rats are administrated ibuprofen after acute exposed to high altitude.Firstly, rats were randomly divided into low altitude group, high altitude group, and hypoxia simulation chamber group, and the blood gas, biochemical and pathological indicators in rats were compared. The results showed that the changes in blood gas, biochemical and pathological indicators in high altitude and hypoxia stimulating chamber groups were almost identical when compared with the low altitude group. The lung tissue of both hypoxia groups had serious hypoxia injury. However, the blood gas and biochemical indicators of high altitude rats and hypoxia stimulating chamber rats were significantly different. These results suggested that we should cautiously interpret the experimental data related with blood gas and biochemical parameters when the data collected from different hypoxia exposure.Secondly, the Antibody Array technology was used to screen the sensitive cytokines of thirty four rat cytokines between high altitude and low altitude groups, and the TIMP-1, MCP-1, TNF-α, IL-1β, IFN-γ were significantly increased. Combined with the literature and previous study, the ELISA and Real-Time PCR technology were used to test and verify the protein and gene expression of sensitive cytokines in rat lung tissue. The results showed that the TIMP-1, MCP-1, TNF-α, IL-1β, and IFN-γ gene expression levels of lung tissue in high altitude group rats were increased 2.09,5.23,1.66,1.75,2.57 times when compared with the low altitude group, and the protein content increased 61.95%,51.01%,30.77%,12.64%,34.52% (all the five cytokines P<0.01).Finally, rats were randomly divided into low altitude group, high altitude group, the high altitude ibuprofen group and high altitude acetazolamide group, and we compared the differences of blood gas and pathological indicators in rats between each group, the protein and gene expression of sensitive cytokines in rat lung tissue were measured. The results showed that the PaO2 in the high altitude ibuprofen group increased 4.83%, the Lac significantly decreased 51.20%when compared with high altitude group (P<0.01). The lung injury in the high altitude ibuprofen group reduced. Real-Time PCR and ELISA results showed that the TIMP-1, MCP-1, TNF-α, IL-1β and IFN-γ gene expression levels in the high altitude ibuprofen group were significantly decreased, while the protein contents in lung tissue were significantly decreased in 4.75%,24.87%,28.09%,16.86%,14.21%,9.16%(all the parameters P<0.01).This study established acute high-altitude exposure rat models. We used Antibody Array technology to screen sensitive cytokines, and verified by ELISA and Real-Time PCR technique. The non-steroidal anti-inflammatory drug ibuprofen was used to study the protective roles of ibuprofen against hypoxia injury. The following conclusion:1. The lung tissue of high altitude and hypoxia stimulating chamber groups had serious hypoxia injury. Compared with the low altitude group, the blood gas, biochemical and pathological in high altitude and hypoxia stimulating chamber groups were almost identical. However, the differences of Blood gas and biochemical indicators were significantly in hypoxia groups.2. When rats were acute exposure to high altitude, the inflammatory response would be activation. The protein and gene expression of TIMP-1、MCP-1、TNF-α、IL-1β、IFN-γ would be increased. Then, the inflammatory cascade expanded. That might be one of the mechanisms of body injury caused by hypoxia.3. Ibuprofen could protect the lung in rat against hypoxia injury after exposed to hypobaric hypoxia. The protective function of ibuprofen against hypoxia injury in rat might relate to the increased PaO2 and the repression of TIMP-1, MCP-1, TNF-α, IL-1β, and IFN-γ.