To establish a mouse model of severe exertional heat stroke-related acute kidney injury (EHS-AKI) in order to provide support for research on the pathogenesis and treatment.

C57BL/6 male wild-type mice aged 6-8 weeks were randomly divided into 6 groups: saline blank control group (n=8), saline-normal temperature-exercise group (n=40), saline-high temperature-high humidity-exercise group (n=80), glycerol blank control group (n=8), glycerol-normal temperature-exercise group (n=40), and glycerol-high temperature-high humidity-exercise group (n=120). The success criteria for modeling EHS included that the mice had rectal temperature ≥ 42.5 ℃ and lost consciousness. At 6 hours, 12 hours, 1 day, 2 days, and 3 days after the exercise, the mice were sacrificed and specimens were taken. Measurement was performed for serum creatinine (Scr), urea nitrogen (BUN), interleukin-6 (IL-6), creatine kinase (CK), myoglobin (MYO), and renal pathological lesions. AKI diagnostic criteria was according to the KDIGO guidelines in Scr elevation ≥ 26.5 within 48 hours μmol/L accompanied by significant renal pathological lesions.

Mice of both the saline-normal temperature-exercise group and the glycerol-normal temperature-exercise group survived at 3 days after exercise without significant change in the renal function. At 6 h, 12 h, 1 d, 2 d, and 3 d after the exercise, the survival rates of the saline-high temperature-high humidity-exercise group were 80%, 70%, 60%, 60%, and 60%, respectively, while the survival rates of the glycerol-high temperature-high humidity-exercise group were 60%, 50%, 40%, 30%, and 30%, respectively. At 12 hours after exercise, in the saline-high temperature-high humidity-exercise group, the level of Scr was briefly increased (P<0.05), while at 6 hours after exercise, in the glycerol-high temperature-high humidity-exercise group, levels of Scr, BUN, IL-6, CK, and MYO significantly increased, and peaked at 1 day after the exercise. In the saline-normal temperature-exercise group, the saline-high temperature-high humidity-exercise group, and the glycerol-normal temperature-exercise group, there were only occasional renal interstitial infiltration of inflammatory cells, without other pathological lesion changes such as renal tubular dilation and edema. In the glycerol-high temperature-high humidity-exercise group, the mice showed loss of brush border of renal tubular epithelial cells, detachment of tubular epithelial cells, exposure of the basement membrane, and tubular cast, etc. At 6 h, 12 h, 1 d, 2 d, and 3 d after exercise, the scores of renal pathological lesions in this group were 0.8±0.5, 1.6±0.6, 3.0±1.1, 1.3±0.5, and 1.1±0.5, respectively.

A mouse model of severe EHS-AKI was successfully established through low-dose glycerol intramuscular injection and exercise in high-temperature and high humidity, which may provide support for further research on the pathogenesis and treatment.