乌司他汀对猪心肺复苏后心肌损伤的保护作用  

Protective effect of ulinastatin on myocardial injury after cardiopulmonary resuscitation in pigs

作　　者：高健[1] 廉明[2] 王娟娟 陈凤英[2] Gao Jian;Lian Ming;Wang Juanjuan;Chen Fengying(Emergency Department of Dalian Central Hospital,Dalian 116033,China;Emergency Department,the Affiliated Hospital of Inner Mongolia Medical University,Huhhot 010059,China)

机构地区：[1]内蒙古医科大学附属医院硕士研究生,呼和浩特010059(现工作单位大连市中心医院急诊科,116033 [2]内蒙古医科大学附属医院急诊科,呼和浩特010059

出　　处：《中华急诊医学杂志》2019年第11期1373-1378,共6页Chinese Journal of Emergency Medicine

基　　金：内蒙古卫生计生委A类一等项目(201701072)。

摘　　要：目的评价乌司他汀(ulinastatin,UTI)对猪心肺复苏后心脏骤停后综合征(post-cardiac arrest syndrome,PCAS)心肌损伤的保护作用。方法3~4个月雄性北京长白猪12只,按随机数字表分为UTI组和对照组,每组各6只,通过程控刺激法复制心室纤颤(室颤)动物模型,室颤5 min后开始CPR,复苏成功11只,UTI组6只和对照组5只。UTI组复苏即刻给予UTI 100000 U溶于生理盐水5 mL,缓慢静推,3 h 1次,直到复苏后24 h(第24 h不给药);对照组复苏开始时即刻缓慢静推生理盐水5 mL作为对照。分别于室颤前基础状态及心肺复苏术后自主循环恢复(restorasion of spontaneous circulation,ROSC)后2、4、6、12、24 h抽取家猪静脉血,采用酶联免疫吸附试验测定肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA),缺血修饰白蛋白(ischemia modified albumin,IMA)。因IMA反应灵敏,升高较快,ROSC后1 h即抽取静脉血检测,余取血点同其余因子。ROSC后24 h处死实验猪,留取心肌组织进行HE染色光镜下观察。采用LSD-t检验和重复测量方差分析进行统计学分析。结果室颤前两组猪炎症因子、氧化应激指标、心肌缺血标志物血清水平指标比较差异均无统计学意义(P>0.05)。室颤后2 h时UTI组TNF-α、IL-6水平明显低于对照组;UTI组4 h时MDA水平明显低于对照组、SOD水平明显高于对照组,差异均有统计学意义(P<0.05);IMA在ROSC后1 h时明显升高,UTI组1 h的水平明显低于对照组,差异有统计学意义(P<0.05),但12 h时两组比较差异已无统计学意义(P>0.05)。组织切片HE染色结果显示,ROSC后24 h时UTI组心肌组织损伤程度明显轻于对照组。结论心肺复苏时应用UTI可以拮抗炎症反应,减轻氧化应激反应,改善心肌组织的损伤,对心肺复苏后心肌损伤具有一定的保护作用。Objective To evaluate the protective effect of ulinastatin(UTI)on myocardial injury after post-cardiac arrest syndrome(PCAS)of cardiopulmonary resuscitation in pigs.Methods Twelve male 3-4 months pigs were randomly divided into two groups,UTI group and control group.The ventricular fibrillation(VF)animal model was replicated by programmed stimulation method.Among the 12 pigs,11 pigs were successfully resuscitated by CPR after 5 min VF,of which,6 pigs were in the UTI group and 5 pigs in the control group.Immediately after resuscitation,pigs in the UTI group was given 100 kU dissolved in 5 mL normal saline with slowly injection every 3 h until 24 h after recovery(no drug was given at 24 h).In the control group,5 mL normal saline was given with same delivery time and frequency as that in the UTI group.The venous blood of the pigs was collected at VF,2,4,6,12,and 24 h after ROCS,and tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),superoxide dismutase(SOD),malondialdehyde(MDA),and ischemia modified albumin(IMA)were measured by enzyme-linked immunosorbent assay(ELISA)method.Because IMA was sensitive and increased rapidly,venous blood was detected at 1 h after ROSC,and the rest test time were same with the rest of the blood factors.Statistical analysis was performed using LSD-t test and variance analysis.The pigs were sacrificed 24 h after ROSC,and specimens from heart tissue were taken for HE staining.Results Before ventricular fibrillation in three groups,there was no significant difference in serum levels of inflammatory cytokines,oxidative stress indexes,and myocardial ischemia markers between the two groups(P>0.05).At 2 h after ventricular fibrillation,the levels of TNF-αand IL-6 level in the UTI group was significantly lower than those in the control group.At 4 h,MDA level in the UTI group was significantly lower than that in the control group(P<0.05);IMA was significantly increased at 1 h after ROSC,and the level of 1 h in the UTI group was significantly lower than that in the control group(P<0.05),but was

关 键 词：乌司他汀 心肺复苏 心脏骤停后综合征 肿瘤坏死因子-α 白细胞介素-6 超氧化物歧化酶 缺血修饰白蛋白 

分 类 号：R54[医药卫生—心血管疾病]