Role of acute hypoxic stress response in the occurrence of high altitude pulmonary edema
Objective To clarify the relationship between acute hypoxic stress response and the occurrence of high altitude pulmonary edema.Methods Male SD rats were randomly divided into control group and metyrapone treatment group.The control group was intraperitoneally injected with normal saline(0.05 mU100 g),and the drug treatment group was intraperitoneally injected with metyrapone(50 mg/kg,0.05 mL/100 g).The two groups were further divided into normoxia group(Xining,atmospheric pressure 582 mmHg,P02 121.6 mmHg)and acute hy-poxia treatment groups for different time(6 h,12 h and 24 h)(simulated altitude of 7 000 m,atmospheric pressure 308 mmHg,PO2 64.3 mmHg).The lung function of rats was detected by DSI-BUXCO non-invasive respiratory function detection system.Evans Blue content determination method was adopted to measure the pulmonary micro-vascular permeability.HE staining was used to observe the morphological variations of lung tissue.The expression of endothelin-1(ET-1)in lung tissue was detected by Western Blot.The serum levels of corticotropin-releasing hormone(CRH)and corticosterone(CORT)were detected by enzyme-linked immunosorbent assay(ELISA).Re-sults ① Compared with the control normoxia group,the tidal volume(TV),minute ventilation(MV)and mid-expi-ratory flow rate(EF50)of the control hypoxia group were significantly reduced(P＜0.05),while airway resistance(Raw)was significantly increased(P＜0.05).Compared with the control hypoxia group,the respiratory rate(FR)of the drug hypoxia group showed a downward trend.② Compared with the control normoxia group,the pulmonary mi-crovascular permeability of the control hypoxia group was significantly increased(P＜0.05).Compared with the drug normoxia group,the pulmonary microvascular permeability of the drug hypoxia group was significantly in-creased(P＜0.05).③ There was exudation of fluid and red blood cells in the alveolar space of the acute hypoxia group.The exudation of alveolar space and interstitial space was the most obvious in the drug hypoxic 24 h group.④ Compared with the control group,the level of serum CRH in the control hypoxia 24 h group was significantly in-creased(P＜0.05).The level of serum CRH in the drug group was significantly higher than that in the control group(P＜0.05).Compared with the control normoxia group,the levels of serum CORT in the control hypoxia groups were significantly increased(P＜0.05).The level of serum CORT in the drug hypoxia group was significantly lower than that in the control hypoxia group(P＜0.05).⑤ Compared with the control normoxia group,the expression of ET-1 in the control hypoxia group was significantly increased(P＜0.05).Compared with the control group,the rela-tive expression of ET-1 in the drug group was significantly increased(P＜0.05).⑥ The expression of ET-1 poly-peptide is positively correlated with the content of Evans Blue in lung tissue and serum CORT.Conclusions The increase of CRH and CORT plays a crucial compensatory role in the stress response induced by acute hypoxia,which might be achieved by inhibiting the release of ET-1 from lung tissue,preventing excessive contraction of hy-poxic pulmonary vessels,thereby protecting the lung microvessels from damage and suppressing the occurrence of pulmonary edema.
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