低体温脓毒症小鼠模型建立及体温变化在急性感染中的意义  

Establishment of a Mouse Model of Hypothermic Sepsis and Significance of Body Temperature Change in Acute Infection

作　　者：李艳萍[1] 黄坤[1] 吕宇飞 黄竞 于久飞[1] LI Yan-Ping;HUANG Kun;LYU Yu-Fei;HUANG Jing;YU Jiu-Fei(Department of Gastroenterology,Civil Aviation General Hospital,Beijing 100123;Beijing Institute of Biotecnology,Beijing 100071,China)

机构地区：[1]民航总医院(北京大学民航临床医学院)消化肿瘤科,北京100123 [2]军事医学研究院生物工程研究所,北京100071

出　　处：《生物技术通讯》2020年第5期554-560,共7页Letters in Biotechnology

基　　金：国家自然科学基金青年基金(31700802)。

摘　　要：目的:建立小鼠稳定脓毒症低温模型并对其温度变化在感染中的意义进行研究。方法:首先用不同剂量志贺菌感染小鼠腹腔,测量体温变化和死亡率;之后通过检测血清中促炎和抗炎的细胞因子水平,对感染后小鼠的炎症反应进行分析,并通过血容量及脏器病理切片评价小鼠感染后机体的损伤;最后,通过对脓毒症小鼠采取提前免疫或抗生素治疗等干预措施,检测不同感染程度下小鼠的存活率和体温变化。结果:随着感染剂量的增加,小鼠体温显著降低,死亡率升高;感染后血清中炎症因子水平升高,其中以促炎因子IL-6和IFN-γ为主,二者均达到104数量级;机体血容量显著降低,并出现肾小管上皮细胞水肿;在感染前给予志贺菌多糖结合疫苗进行预防性和感染后给予卡那霉素进行治疗性干预后,小鼠存活率均明显提升,同时低体温症状得到显著缓解。结论:通过小鼠腹腔感染病原细菌能够建立稳定的低温脓毒症模型,为脓毒症导致体温过低研究提供思路;同时,体温的变化与小鼠感染程度及存活率具有相关性,可作为判断脓毒症严重程度的便捷的指标和依据。Objective:To establish a stable hypothermia model of sepsis and study the significance of temperature change in sepsis.Methods:At first, the mice were injected intraperitoneally with different doses of Shigella,and the changes of body temperature and mortality were measured. Then, the levels of pro-inflammatory and antiinflammatory cytokines in serum were detected to analyze the inflammatory response of mice after infection. The injuries were evaluated by blood volume and pathological sections of organs. Finally, the survival rate and body temperature of mice with sepsis were detected by different treatment, immunized with Shigella conjugate vaccine in advance or injected kanamycin after infection.Results:With the increase of infection dose, the body temperature decreased significantly, and the mortality increased. Then, the level of inflammatory factors in serum increased after infection, especially pro-inflammatory factors such as IL-6 and IFN-γ reached over 104. Further, the blood volume decreased significantly and edema of renal tubular epithelial cells in infected mice. In addition, after prevention with vaccine or therapy with antibiotic, the survival rates of mice were significantly increased, and the symptoms of hypothermia were significantly relieved.Conclusion:The stable model of hypothermia sepsis can be established by intraperitoneal infection of pathogenic bacteria in mice, which provides ideas for the study of hypothermia caused by sepsis. At the same time, the change of body temperature is related to the degree of infection and survival rate of mice, which can be used as a convenient index and basis for judging the severity of sepsis.

关 键 词：脓毒症 低体温 小鼠模型 急性感染 

分 类 号：R631[医药卫生—外科学]