摘要
目的比较两种温度策略建立的伴多器官功能障碍综合征(MODS)经典型热射病(CHS)小鼠模型的差异。方法将66只雄性C57BL/6J小鼠采用随机数字表法分为直接热打击(DHS)组(n=28)、逐步升温热打击(SHS)组(n=28)及对照组(n=10)。前两组分别使用41℃直接打击法及25.0~39.5℃逐步升温法建立CHS小鼠模型。将小鼠放入模拟气候舱,密切观察其活动规律及意识状态,并监测直肠温度(Tr),待达到造模终点后出舱。每组采用随机数字表法抽取4只小鼠,于热暴露结束后恢复24 h取其血样和肝、肾、肠、肺、脾组织,采用全自动生化分析仪检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酐(CREA)、血尿素氮(BUN)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)和肌酸激酶同工酶MB(CK-MB)水平,采用多因子检测试剂盒测定白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、单核细胞趋化蛋白(MCP)-1及转化生长因子(TGF)-β水平,并对小鼠不同器官进行组织学观察及病理损伤评分;对剩余小鼠进行72 h生存分析。结果两种热打击策略均可成功建立CHS小鼠模型,但与DHS组比较,SHS组小鼠热暴露的时间较长[(181.61±41.88)min vs.(104.72±18.68)min,P<0.001],脱水百分比较高[(11.59±1.52)%vs.(7.07±1.84)%,P<0.001],72 h内致死率较高(73.68%vs.22.22%,P<0.05)。恢复24 h后,SHS组ALT、AST、CREA、BUN水平均明显高于DHS组[(875.63±241.24)U/L vs.(139.38±188.22)U/L,P<0.01;(2406.75±1008.69)U/L vs.(208.13±149.23)U/L,P<0.01;(79.88±41.39)U/L vs.(18.75±10.51)U/L,P<0.05;(134.33±52.54)U/L vs.(17.75±7.31)U/L,P<0.01],各器官组织病理学评分均明显高于DHS组(P<0.05);此外,SHS组MCP-1水平明显高于DHS组[(22.89±1.97)pg/ml vs.(15.97±3.91)pg/ml,P<0.05],TGF-β水平明显低于DHS组[(936.46±30.17)pg/ml vs.(1453.50±129.81)pg/ml,P<0.001]。结论使用逐步升温法建立的CHS小鼠模型成功率及致死率均较高,各器官损伤较重,是一种更符合CHS病理生理状态的动物�
Objective To examine the differences between mouse models of classic heat stroke(CHS)with multiple organ dysfunction via two different rising strategies.Methods A total of 66 male C57BL/6J mice were divided into direct heat stroke(DHS)group(n=28),a stepwise heat stroke(SHS)group(n=28),and control group(n=10)using the random number table method.In the first two groups,animals received direct warming at 41℃and stepwise warming from 25.0℃to 39.5℃,using a simulated climate chamber,respectively.While the animals were in the climate chamber before reaching the endpoint,we constantly monitored the animal activity,animal consciousness,and rectal temperature.We randomly selected 4 animals from each group and collected the blood samples and organ tissues(liver,kidney,intestine,lung,and spleen)after 24 hours of recovery since the end of heat exposure.We used the automatic biochemical analyzer to measure the levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine(CREA),blood urea nitrogen(BUN),alkaline phosphatase(ALP),lactate dehydrogenase(LDH),and creatine kinase isoenzyme MB(CKMB).We employed multifactorial test kits to detect the levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,monocyte chemoattractant protein(MCP)-1 and transforming growth factor(TGF)-β.We analyzed the histological sections from each organ and then calculated the pathological injury scores.We saved the remaining mice for the 72 h survival analysis.Results Both heat stroke strategies can establish a stable CHS model of the mouse.In contrast with mice in DHS group,mice in SHS group exposed to heat for a longer time[(181.61±41.88)min vs.(104.72±18.68)min,P<0.001],had a higher percentage of dehydration[(11.59±1.52)%vs.(7.07±1.84)%,P<0.001]and higher 72 h mortality(73.68%vs.22.22%,P<0.05).After 24 hours'recovery,biochemical indicators(ALT,AST,CREA,BUN)of SHS group were higher than those of DHS group[(875.63±241.24)U/L vs.(139.38±188.22)U/L,P<0.01;(2406.75±1008.69)U/L vs.(208.13±149.23)U/L,P<0.01
作者
刘育妍
李云
胡婕
宣律
王陆
袁睿
邓子辉
张玉想
康红军
Liu Yu-Yan;Li Yun;Hu Jie;Xuan Lv;Wang Lu;Yuan Rui;Deng Zi-Hui;Zhang Yu-Xiang;Kang Hong-Jun(Medical School of Chinese PLA,Beijing 100853,China;Department of Critical Care Medicine,the First Medical Center of Chinese PLA General Hospital,Beijing,100853,China;Graduate School of Hebei North University,Zhangjiakou,Hebei 075000,China;Department of Biochemistry,Chinese PLA Medical School,Beijing 100853,China;Department of Critical Care Medicine,the Eighth Medical Center of Chinese PLA General Hospital,Beijing 100091,China)
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2023年第8期893-902,共10页
Medical Journal of Chinese People's Liberation Army
基金
军委科技委基础加强计划(军173)重点基础研究项目(2022-JCJQ-ZD-097-11)。
