Establishment of an acute plateau hypoxia lung tissue injury model of male rats and exploration of the mechanisms of plateau hypoxia lung tissue injury
Objective To establish an acute plateau hypoxia lung tissue injury model of male rats by relevant parameters,and to explore the mechanism of plateau hypoxia lung tissue injury.Methods 1.Establishment of acute plateau hypoxia lung tissue injury model of male rats:male rats were divided into 5 groups,i.e.,blank control group,plateau hypoxia groups of 6 h,24 h,48 h and 72 h.The model was entered into a low-pressure oxygen chamber(sim-ulating an altitude of 7 000 m)after 7 days of adaptive feeding.The successful modeling was judged based on blurred lung tissue texture,thickening of alveolar walls and widening of alveolar septa.2.Mechanisms of high alti-tude hypoxia lung injury:the results of arterial blood gas analysis,the content of angiotensin Ⅱ(Ang Ⅱ),the content of endothelin 1(ET-1),the expression of angiotensin-converting enzyme(ACE)mRNA and the ultrastructure of the lung tissue of each group were compared.Correlation analysis was conducted as well.Results 1.The variations in the arterial blood gas-related indexes of male rats in each group:compared with the control group,the values of partial pressure of oxygen(PaO2),arterial oxygen saturation(SaO2),partial pressure of carbon dioxide(PaCO2)and acid-base(pH)of plateau hypoxia groups of 6 h,24 h,48 h and 72 h all decreased.The longer the hypoxia time,the more obvious the decrease was in a certain range of time(P＜0.05).2.The variations in lung histomorphology:com-pared with the control group,light microscopy showed different degrees of lung texture variations,alveolar wall thickening and widening of alveolar septum in all plateau hypoxia groups;the lung tissue damage gradually aggra-vated with the prolongation of the time with hypoxia.3.Variations of content of Ang Ⅱ and ET-1 in lung tissue of rats in each group:compared with the control group,the content of Ang Ⅱ and ET-1 in lung tissue of rats in each group of plateau hypoxia increased significantly(P＜0.01),and reached the peak in the 72h group with the prolon-gation of the time of hypoxia within a certain time frame.4.Comparisons of ACE mRNA expression in lung tissue of rats in each group:compared with the control group,the expression of ACE mRNA was up-regulated in lung tis-sue of rats in all groups.Besides,it was significantly elevated in the 6h group and reached the peak in the 72h group(P＜0.01).Conclusion Simulating an altitude of 7 000 m by using a low-pressure oxygen chamber can effec-tively establish a rat lung injury model;the mechanism of plateau hypoxia lung injury may be related to the up-regulation of the expression levels of ET-1,Ang Ⅱ and ACE mRNA as well as the imbalance of the renin-angio-tensin system(RAS).
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