关键词: SD大鼠, 高原实地, 模拟高原, 肺水肿, 比较研究

Abstract: Objective　To establish high altitude pulmonary edema (HAPE) model by subjecting SD rats to treadmill exercise under various conditions (altitude platform, hypoxia duration, and altitude) and to conduct a differential analysis.Methods　Ninety SD rats were randomly divided into 9 groups, namely a control group and 8 experimental groups (n=10). The 8 experimental groups were exposed to 4 environments [high altitude field (4 010 m) or simulated high altitude environments (4 000, 5 000, 6 000 m)] for 2 time points (48 h or 72 h), and assisted treadmill exhaustive exercise was performed to establish the HAPE model. The control group was not exposed to hypoxic environment. After the exposure period, relevant physiological and pathological indicators related to high altitude were immediately collected and measured.Results　Compared with control group, rats in all experimental groups exhibited varying degrees of lung lesions. The protein concentration, creatinine (Cr), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) were significantly elevated (P<0.05, P<0.01). Urea (UREA), partial pressure of carbon dioxide (PaCO2 ), partial pressure of oxygen (PaO2 ), base excess (BE), extracellular fluid base excess (BEecf ), superoxide dismutase (SOD), glucose (Glu), and interferon-γ (INF-γ) were significantly decreased (P<0.01). In all experimental groups except for the simulated 4000 m/48 h group, the lung water content (LWC), red blood cell count (RBC), white blood cell count (WBC), and monocyte chemotactic protein 1,MCP-1) protein-1 (MCP-1) in lung tissue were significantly increased (P<0.05, P<0.01). In all experimental groups except for the simulated 4000 m/48 h group and the field 48 h group, malondialdehyde (MDA) was significantly elevated (P<0.05, P<0.01). In the field 48 h group, simulated 5 000 m/48 h group, and simulated 6 000 m/48 h group, hypoxia-inducible factor 1α (HIF-1α) were significantly increased (P<0.01), while endothelin-1 (Edn1) were significantly decreased (P<0.05, P<0.01). In the field 72 h group, simulated 5 000 m/72 h group, and simulated 6000 m/72 h group, vascular endothelial growth factor A (Vegfa) and endothelial PAS domain protein 1 (Epas1) were significantly elevated (P<0.05, P<0.01), and peroxisome proliferator-activated receptor α (Ppara) were significantly decreased (P<0.05).Conclusion　Combined with treadmill exercise, exposure to high altitude (4 010 m) for 48 h or 72 h in the field, or exposure to simulated high altitude (5 000 m or 6 000 m) for 48 h or 72 h, has a high success rate and is relatively stable in establishing a high altitude pulmonary edema model, making it suitable for promotion.

Key words: SD rats, plateau, simulated plateau, pulmonary edema, differential research