一种重型劳力性热射病相关急性肾损伤小鼠模型的建立与探讨  

Establishment and exploration of a mouse model of severe exertional heat stroke-related acute kidney injury

作　　者：李青霖[1] 宋仁杰 周飞虎[1,2] Li Qinglin;Song Renjie;Zhou Feihu(Department of Critical Care Medicine,First Medical Center of Chinese PLA General Hospital;First Medical Center of Chinese PLA General Hospital,State Key Laboratory of Kidney Diseases,Beijing 100853,China)

机构地区：[1]解放军总医院第一医学中心重症医学科,北京100853 [2]解放军总医院第一医学中心肾脏疾病国家重点实验室

出　　处：《中华肾病研究电子杂志》2023年第5期265-270,共6页Chinese Journal of Kidney Disease Investigation（Electronic Edition）

基　　金：基础加强计划项目(2022-JCJQ-ZD-097-11)。

摘　　要：目的: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。方法: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≥26.5μmol/L并伴有明显的肾脏病理损伤。结果: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)。结论: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。Objective 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.Methods 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 hoursμmol/L accompanied by significant renal pathological lesions.Results 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-

关 键 词：劳力性热射病 急性肾损伤 动物模型 小鼠 

分 类 号：R692[医药卫生—泌尿科学]