尿胰蛋白酶抑制剂对热射病大鼠神经系统损伤保护作用机制研究  

Protective mechanism of urinaty trypsin inhibitor on nervous system injury of heatstroke rats

作　　者：王丽南 王宏 时倩 孙香蕾 李楠[1] 葛凤 金红旭 高燕 WANG Li-nan;WANG Hong;SHI Qian;SUN Xiang-lei;LI Nan;GE Feng;JIN Hong-xu;GAO Yan(Department of Emergency,General Hospital of Northern Theater Command,Shenyang 110016,China)

机构地区：[1]北部战区总医院急诊医学部,辽宁沈阳110016

出　　处：《创伤与急危重病医学》2022年第2期83-87,共5页Trauma and Critical Care Medicine

基　　金：重症多发伤重要脏器功能保护研究(CSY12J002)。

摘　　要：目的通过建立热射病大鼠模型,探讨尿胰蛋白酶抑制剂(UTI)对热射病大鼠神经系统的保护作用及其机制。方法选取雄性健康清洁级SD大鼠30只,体质量为(225±25)g,随机分为空白对照组(n=10)、热射病模型组(n=10)与药物治疗组(n=10)。空白组大鼠置于常温下;热射病模型组、药物治疗组大鼠麻醉后置于温度为42℃、湿度为(60%±5%)的人工气候箱内,建立热射病大鼠模型。空白组大鼠尾静脉注射10 ml/kg生理盐水干预;热射病大鼠建模成功后,热射病模型组大鼠经尾静脉注射10 ml/kg生理盐水干预,药物治疗组大鼠经尾静脉给予100000 U/kg(将100000 U的UTI溶于10 ml生理盐水内)的UTI进行干预。常温观察4 h后再次麻醉,予以腹主动脉采血,并解剖留取大鼠脑组织。采用酶联免疫吸附法检测血清肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)及热休克蛋白70(HSP70)的表达。采用蛋白印迹杂交法检测大鼠脑组织中HSP70的表达。通过光镜苏木素-伊红(HE)染色观察脑组织神经元细胞损伤情况。结果热射病模型组血清HSP70、TNF-α、IL-1β水平明显高于空白对照组;药物治疗组血清TNF-α、IL-1β水平低于热射病模型组,血清HSP70水平高于热射病模型组,差异均有统计学意义(P<0.05)。热射病模型组大鼠脑组织HSP70蛋白表达量高于空白对照组,神经元细胞数少于空白对照组;药物治疗组大鼠脑组织HSP70蛋白表达量、神经元细胞数高于热射病模型组,差异均有统计学意义(P<0.05)。结论UTI可通过诱导HSP70超表达,加强抑制炎症因子的作用,进而对热射病神经系统起到保护作用。Objective To investigate the protective effect and mechanism of urinary trypsin inhibitors(UTI)on the nervous system of heatstroke rats by establishing a model of heatstroke rats.Methods A total of 30 male healthy and clean SD rats with a body mass(225±25)g were randomly divided into blank control group(n=10),heatstroke model group(n=10),and drug treatment group(n=10).The rats in the blank control group were placed at room temperature,and the rats in the heatstroke model group and the drug treatment group were anesthetized and placed in an artificial climate box with a temperature of 42℃and humidity(60%±5%)to establish the heatstroke rat models.The rats in blank control group were injected 10 ml/kg of normal saline through the tail vein.After successfully modeling heatstroke rats,the rats in the heatstroke model group were injected 10 ml/kg of normal saline through the tail vein,and the rats in the drug treatment group were given a UTI of 100000 U/kg(100000 U UTI dissolved in 10 ml normal saline)through the tail vein for intervention.After 4 h of observation at room temperature,the rats were anesthetized again,the blood of the rats were collected from the abdominal aorta,and the brain tissues of the rats were dissected.The levels of serum tumor necrosis factorα(TNF-α),interleukin 1β(IL-1β),and heatstroke protein 70(HSP70)were detected by enzyme-linked immunosorbent assay.Western blot hybridization was used to detect the expression of HSP70 in rat brain tissue.Neuronal cell damages in brain tissues were observed by photomicroscopic hematoxylin-eosin(HE)staining.Results The levels of serum HSP70,TNF-αand IL-1βin the heatstroke model group were significantly higher than those in the blank control group.The levels of serum TNF-αand IL-1βin the drug treatment group were lower than those in the heatstroke model group,and the level of serum HSP70 was higher than that in the heatstroke model group,and the differences were statistically significant(P<0.05).The expression of HSP70 protein in rat brain tissue in

关 键 词：热射病 热休克蛋白70 尿胰蛋白酶抑制剂 神经系统损伤 

分 类 号：R594.1[医药卫生—内科学] R747.9[医药卫生—临床医学]