建立小鼠重型劳力性热射病-急性肾损伤(EHS-AKI)模型，为其发病机制及相关治疗研究提供支持。

6~8周的C57BL/6雄性野生型小鼠随机分为6组：生理盐水空白对照组(n＝8)、生理盐水常温运动组(n＝40)、生理盐水高温高湿运动组(n＝80)；甘油空白对照组(n＝8)、甘油常温运动组(n＝40)、甘油高温高湿运动组(n＝120)。EHS的建模成功标准：小鼠直肠温度≥42.5℃且意识丧失。运动结束后6 h、12 h、1 d、2 d和3 d处死小鼠，留取标本。检测肌酐(Scr)，尿素氮(BUN)，白介素-6(IL-6)，肌酸激酶(CK)、肌红蛋白(MYO)和肾脏病理。AKI诊断标准：参照KDIGO指南，48 h内Scr升高≥ 26.5 μmol/L并伴有明显的肾脏病理损伤。

生理盐水常温运动组和甘油常温运动组小鼠至3 d时均存活，肾功能无明显变化。在运动结束后6 h、12 h、1 d、2 d、3 d，生理盐水高温高湿运动组的小鼠生存率分别为80%、70%、60%、60%、60%，而甘油高温高湿运动组的小鼠生存率则分别为60%、50%、40%、30%、30%。运动后12 h，生理盐水高温高湿运动组小鼠的Scr短暂性升高(P<0.05)；运动后6 h，甘油高温高湿组小鼠的Scr、BUN、IL-6、CK、MYO即显著升高，在运动后1 d达到峰值。在生理盐水常温运动组、生理盐水高温高湿运动组、甘油常温运动组的小鼠，偶见肾间质炎症细胞浸润，未见肾小管扩张、水肿等肾脏损伤病理改变。甘油高温高湿运动组小鼠出现肾小管上皮细胞刷状缘脱失、小管上皮细胞脱落、基底膜裸露、管腔内管型等，其在运动后6 h、12 h、1 d、2 d、3 d时肾脏病理损伤的评分分别为(0.8±0.5)、(1.6±0.6)、(3.0±1.1)、(1.3±0.5)和(1.1±0.5)。

通过小剂量甘油肌注和高温高湿运动，成功建立了重型EHS-AKI小鼠模型，将可为其发病机制及相关治疗研究提供支持。

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.