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

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.