鸢尾素通过改善下丘脑视前区热敏神经元功能减轻EHS器官损伤的作用及机制研究  

Irisin alleviates organ damage caused by exertional heat stroke through improving the function of warm sensitive neurons in the hypothalamic preoptic area

作　　者：李婧 范仲敏 彭宇亮 周子清 尹路 吴优 马宏炜 张西京 Li Jing;Fan Zhongmin;Peng Yuliang;Zhou Ziqing;Yin Lu;Wu You;Ma Hongwei;Zhang Xijing(Department of Critical Care Medicine/Department of Anesthesiology and Perioperative Medicine,Xijing Hospital,Air Force Medical University,Xi'an 710032,China;Department of Microbiology,School of Basic Medicine,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]空军军医大学西京医院重症医学科/麻醉与围术期医学科,西安710032 [2]空军军医大学基础医学院微生物学与病原生物学教研室,西安710032

出　　处：《国际麻醉学与复苏杂志》2023年第12期1272-1280,共9页International Journal of Anesthesiology and Resuscitation

摘　　要：目的明确鸢尾素改善劳力型热射病(exertional heat stroke,EHS)的作用并探讨相关机制。方法以119只野生型雄性C57BL/6小鼠为研究对象。①将30只小鼠按随机数法分为2组(每组15只):常温对照组(SHE组)和EHS组。SHE组常规训练6 d、休息2 d后在(25.0±1.0)℃、(40±5)%湿度的常温环境下运动,EHS组常规训练6 d、休息2 d后在(38.0±1.0)℃、(70±5)%湿度的恒温高湿环境运动舱内运动造模。记录各组小鼠的核心体温、起病及恢复时间、7 d生存率,采用H-E染色观察脑、肝、肾组织病理变化及尼氏染色计算存活细胞数,行为学实验检测自主活动和探索能力。②将18只小鼠按随机数表法分为3组(每组6只):SHE组、EHS组和热习服(heat acclimation,HA)组(HA组)。SHE组、EHS组造模方法见①,HA组在(35.0±1.0)℃、(70±5)%湿度的恒温高湿环境运动舱中进行14 d的运动训练。利用ELISA法检测各组小鼠血清鸢尾素浓度。③将63只小鼠按随机数表法分为3组(每组21只):生理盐水+EHS组(NS+EHS组)、鸢尾素+EHS组(Irisin+EHS组)、HA+EHS组。NS+EHS组在EHS造模前7 d开始给予生理盐水注射,Irisin+EHS组在造模前7 d开始给予鸢尾素注射,Irisin+EHS组在造模前7 d开始给予鸢尾素注射。记录各组核心体温、起病及恢复时间、7 d生存率,采用H-E染色观察组织病理变化,行为学实验检测自主活动和探索能力。④将8只小鼠按随机数表法分为2组(每组4只):NS+EHS和Irisin+EHS组(干预方式见③)。2组分别在造模30 min、60 min时取脑组织采用免疫荧光染色检测神经元c-Fos表达情况。电生理检测鸢尾素灌流前后下丘脑视前区(hypothalamic preoptic area,POA)热敏神经元兴奋性突触后电流(excitatory post-synaptic current,EPSC)的频率和振幅变化。结果与SHE组比较,EHS组平均在70 min发生热射病,核心体温升高,7 d生存率降低(P<0.05);各器官出现明显的病理损伤,存活细胞数减少(P<0.05);进入旷场中Objective To determine the effect of irisin on improving exertional heat stroke(EHS)and explore related mechanisms.Methods One hundred and nineteen wild-type male C57BL/6 mice were used as research subjects.①Divide 30 mice into 2 groups according to the random number table method(n=15):the SHE group and the EHS group.After 6 days of routine training and 2 days of rest,the SHE group ran at room temperature at(25.0±1.0)℃and(40±5)%humidity;after 6 days of routine training and 2 days of rest,the EHS group ran in a constant temperature and high humidity environment at(38.0±1.0)℃and(70±5)%humidity to create a model.Record the core body temperature,onset and recovery time,and 7-day survival rate of each group of mice.Observe the pathological changes in brain,liver,and kidney tissues using H-E staining and calculate the number of surviving cells using Nissl staining.Conduct behavioral experiments to detect autonomous activity and exploration ability.②Divide 18 mice into 3 groups according to the random number table method(n=6):SHE group,EHS group,and heat acclimation(HA)group.The modeling methods for SHE group and EHS group were shown in①.The HA group underwent 14 days of running training in a constant temperature and high humidity environment exercise chamber at(35.0±1.0)℃and(70±5)%humidity.Enzyme-linked immunosorbent assay(ELISA)method was used to detect the serum concentration of irisin in each group of mice.③Divide 63 mice into 3 groups according to the random number table method(n=21):physiological saline+EHS group(NS+EHS group),irisin+EHS group(Irisin+EHS group),and HA+EHS group.The NS+EHS group received saline injection 7 days prior to EHS modeling.The Irisin+EHS group received irisin injection starting 7 days before modeling;The Irisin+EHS group received irisin injection starting 7 days before modeling.Record core body temperature,onset and recovery time,7-day survival rate,observe tissue pathological changes using H-E staining,and conduct behavioral experiments to test autonomous activity and

关 键 词：劳力型热射病 热习服 鸢尾素 下丘脑视前区 热敏神经元 

分 类 号：R96[医药卫生—药理学]