高原自然环境下高原红细胞增多症动物模型的建立^*

Establishment of an Animal Model of High-altitude Polycythemia Under Natural Plateau Environment

摘要

目的 探索在高原自然环境（海拔3 650 m，西藏拉萨）下建立高原红细胞增多症（high-altitude polycythemia, HAPC）动物模型所需的时间及发病率，为高原疾病相关研究提供实验技术支撑。方法 将自平原（四川成都，平均海拔500 m）购入的40只SPF级SD大鼠（雌雄各20只）运至拉萨（海拔3 650 m）常规饲养。进入高原后第1周每日采用血常规仪（Sysmex XS-500i）检测血常规，第2周起每周检测1次；同时每日使用动物体重秤监测体质量。参照“青海标准”（女性血红蛋白≥190 g/L，男性≥210 g/L）判断造模是否成功。结果 在高原自然环境下常规饲养40 d（动物房温度17～25 ℃，相对湿度40%～70%），雌性SD大鼠血红蛋白平均值达202 g/L（SE=2.55），雄性达217 g/L（SE=2.291），造模成功。雌性造模成功率为77%（14/18），高于雄性的42%（6/14）。造模成功大鼠出现畏寒喜暖、反应迟钝、蜷缩少动、被毛蓬松无光泽、唇舌爪尾皮肤黏膜紫黯等异常表现。与平原对照相比，进入高原后大鼠的血红蛋白、红细胞计数、红细胞压积、红细胞分布宽度、平均红细胞体积、淋巴细胞百分比等指标差异有统计学意义（P<0.05）。雌性大鼠体重增长低于雄性（P<0.001）。Hb浓度升高与血压上升趋势一致，但差异无统计学意义（P>0.05）。结论 在海拔3 650 m高原自然条件下常规饲养40 d可成功构建HAPC动物模型，雌性SD大鼠的造模成功率高于雄性。

Abstract

Objective To explore the time course and incidence of establishing an animal model of high-altitude polycythemia (HAPC) under a natural plateau environment (Lhasa, Xizang, 3 650 m above sea level) and to provide experimental technical support for high-altitude disease research. Methods Forty SPF grade Sprague-Dawley rats (20 males and 20 females) purchased from a low-altitude area (Chengdu, Sichuan, average altitude 500 m) were transported to Lhasa (3 650 m) and conventionally reared. A hematology analyzer (Sysmex XS-500i) was used to measure blood parameters daily during the first week after arrival and weekly thereafter; body mass was monitored daily with a precision electronic scale. Model success was determined according to the “Qinghai Criteria” (hemoglobin ≥ 190 g/L in females, ≥ 210 g/L in males). Results After 40 days of conventional rearing under natural plateau conditions (animal room temperature 17-25 °C, relative humidity 40%-70%), the mean hemoglobin (Hb) level reached 202 g/L (SE = 2.55) in females and 217 g/L (SE = 2.291) in males, indicating successful modeling. The success rate was higher in females (77%, 14/18) than in males (42%, 8/19). Successfully modeled rats exhibited behavioral abnormalities such as cold aversion, preference for warmth, reduced responsiveness, curled-up posture with less movement, ruffled and lusterless fur, and purplish-dark discoloration of the skin and mucous membranes of the lips, tongue, paws, and tail. Compared with plain controls, Hb, red blood cell count (RBC), hematocrit (HCT), red blood cell distribution width (RDW), mean corpuscular volume (MCV), and lymphocyte percentage (LYMPH%) showed statistically significant differences after entering the plateau (P < 0.05). Body weight gain was lower in females than in males ( P < 0.001). The increase in Hb concentration was consistent with the upward trend of blood pressure, but the difference was not statistically significant ( P > 0.05). Conclusion Conventional rearing for 40 days under natural plateau conditions at 3 650 m can successfully establish an HAPC animal model in SD rats, with a higher success rate in females than in males.

关键词

高原自然环境 / 高原红细胞增多症 / 动物模型 / 血常规

Key words

High-altitude natural environment / High-altitude polycythemia / Animal model / Blood routine

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基金资助

*2023年度西藏自治区科技厅“揭榜挂帅”项目(XZ202303ZY0008G)

国家自然科学基金项目(82241023)

四大慢病重大专项(2025ZD0551811)

2024年度西藏自治区科技厅联合资助项目(XZ202403ZY0006)

日喀则市2024年区域科技协同创新专项项目(QYXTZX-RKZ2024-01-1)

日喀则市2025年度科技计划项目(RKZ2025ZD-003)

2024年度拉萨市科技局资助项目(LSKJ202466)

2026年拉萨市科技局计划项目(LSKJ202644)

西藏大学学科领军人才项目(0061243/047)