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

摘要： 目的　使用SD大鼠在不同条件(缺氧平台、缺氧时间、海拔高度)组合下进行跑台运动来建立高原肺水肿模 型,并进行差异性分析。方法　90只SD大鼠随机分为9组,即空白对照组和8个实验组(n=10),将8个实验组分 别在4种环境[高原实地(4 010 m)或模拟高原环境(4 000、5 000、6 000 m)]暴露2个时间点(48 h或72 h),并辅 助跑台力竭运动,来建立高原肺水肿模型,空白对照组不在低氧环境中暴露。暴露时间结束后,立即采集并测定高 原生理病理相关指标。结果　与空白对照组相比,各实验组大鼠肺部均产生不同程度病变,肺部肺泡灌洗液蛋白 浓度(BALF)、肌酐(Cr)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)均显著升高(P<0.05, P<0.01);尿素 (UREA)、二氧化碳分压(PaCO2 )、氧分压(PaO2 )、碱剩余(BE)、细胞外液碱剩余(BEecf )、超氧化物歧化酶(SOD)、 葡萄糖(Glu)和干扰素 γ(INF-γ)均显著降低(P<0.01);除模拟4 000 m/48 h组外的各实验组肺部肺组织含水量 (LWC)、红细胞计数(RBC)、白细胞计数(WBC)、单核细胞趋化蛋白-1(MCP-1)均显著升高(P<0.05, P<0.01);除 模拟4 000 m/48 h组和实地48 h组外,其他实验组的丙二醛(MDA)均显著升高(P<0.05, P<0.01);实地48 h组、 模拟5 000 m/48 h组和模拟6 000 m/48 h组的缺氧诱导因子 1α(HIF-1α)显著升高(P<0.01),内皮素-1(Edn1)显 著降低(P<0.05, P<0.01);实地72 h组、模拟5 000 m/72 h组和模拟6 000 m/72 h组的血管内皮生长因子 A (Vegfa)、内皮PAS结构域蛋白1(Epas1)显著升高(P<0.05, P<0.01),过氧化物酶体增殖物激活受体 α(Ppara)显 著降低(P<0.05)。结论　结合跑台运动条件下,高原实地(4 010 m)暴露48 h或72 h,模拟高原海拔(5 000 m或 6 000 m)暴露48 h或72 h建立高原肺水肿模型较为稳定,适合推广。

关键词: SD大鼠, 高原实地, 模拟高原, 肺水肿, 比较研究