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丁酸钠减轻心肺复苏后肾肠损伤作用及机制的实验研究

The effect and mechanism of sodium butyrate on alleviating renal and intestinal injury after cardiopulmonary resuscitation
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摘要 目的探讨丁酸钠(sodium butyrate,NaB)对心脏骤停心肺复苏(cardiac arrestcardiopulmonary resuscitation,CA-CPR)后肾肠器官损伤的作用及相关机制。方法采用随机数字表法,将24头国产健康雄性白猪随机分为3组:假手术组(sham,n=6)、CA-CPR组(n=10)与NaB组(n=8)。Sham组动物仅进行操作准备,CA-CPR组和NaB组动物以心室电刺激诱发心室颤动9 min后CPR 6 min的方法制备猪CA-CPR模型。于复苏后5 min时,NaB组经静脉泵入NaB 75mg/kg、时长1 h,Sham组和CA-CPR组则经静脉泵入等量溶媒。于复苏后1 h、2 h、4 h和24 h时,采集血样检测肾肠损伤指标如肌酐(creatinine,Cr)、尿素氮(blood urea nitrogen,BUN)、肠型脂肪酸结合蛋白(intestinal fatty acid binding protein,IFABP)和二胺氧化酶(diamine oxidase,DAO)的血清水平。于复苏后24 h时,获取肾肠组织标本检测自噬标志蛋白如微管相关轻链蛋白3Ⅱ(microtubule-associated protein light chain 3,LC3Ⅱ)和p62的蛋白表达水平,以及检测肾肠组织细胞的凋亡程度。使用SPSS软件进行统计学分析,组间比较采用单因素方差分析。结果CACPR组和NaB组在经历CA-CPR过程后,肾肠损伤指标Cr、BUN、IFABP和DAO在复苏后各时间点的血清水平均明显高于Sham组,组间比较差异有统计学意义(均P<0.05)。NaB组上述各时间点的肾肠损伤指标血清水平均明显低于CA-CPR组,组间比较差异有统计学意义[Cr(μmol/L):1 h为(90±5)vs.(127±9),2 h为(135±14)vs.(168±9),4 h为(174±10)vs.(211±12),24 h为(192±10)vs(.253±13);BUN(mmol/L):1 h为(10.5±1.0)vs(.12.3±1.0),2 h为(12.2±1.2)vs.(15.3±0.9),4 h为(13.6±1.3)vs.(18.3±1.2),24 h为(15.4±1.4)vs.(21.5±1.4);IFABP(pg/mL):1 h为(502±33)vs.(554±32),2 h为(574±52)vs.(644±41),4 h为(646±44)vs.(732±43),24 h为(711±42)vs.(828±42);DAO(U/mL):1 h为(8.6±1.0)vs.((10.5±0.9),2 h为(10.6±1.2)vs.(12.8±1.0),4 h为(12.1±1.0)vs.(15.0±1.0),24 h为(14.1±1.1)vs.(17.6±1.0),均P<0.05]。肾肠组织的检测分析显示,CA-CPR组� Objective To investigate the effect of sodium butyrate(NaB)on renal and intestinal injury after cardiac arrest and cardiopulmonary resuscitation(CA-CPR)and its related mechanism.Methods Twenty-four domestic healthy male swines were randomly divided into 3 groups:sham group(n=6),CA-CPR group(n=10)and NaB group(n=8).The animals only underwent operational preparation in the sham group.The animal model of CA and CPR was established by 9 min of ventricular fibrillation induced by electrical stimulation in the ventricle and then 6 min of CPR in the CA-CPR and NaB groups.At 5 min after resuscitation,a dose of 75 mg/kg of NaB was intravenously infused for 1 h in the NaB group,and meanwhile the same volume of vehicle was intravenously infused in the sham and CA-CPR groups.At 1,2,4,and 24 h after resuscitation,blood samples were collected to detect the renal and intestinal injury biomarkers,such as creatinine(Cr),blood urea nitrogen(BUN),intestinal fatty acid binding protein(IFABP),and diamine oxidase(DAO).At 24 h after resuscitation,renal and intestinal tissue specimens were harvested to detect the protein markers of cell autophagy including microtubuleassociated protein light chain 3Ⅱ(LC3Ⅱ)and p62 expression,and also renal and intestinal apoptosis.Statistical analysis was performed by SPSS software,and continuous variables were compared with oneway analysis of variance among the groups.Results After CA-CPR,the renal and intestinal injury biomarkers including Cr,BUN,IFABP,and DAO were significantly increased at all time points after resuscitation in the CA-CPR and NaB groups compared with the sham group(all P<0.05).The injury biomarkers mentioned-above were significantly lower at all time points after resuscitation in the NaB group than in the CA-CPR group[Cr(μmol/L):(90±5)vs.(127±9)at 1 h,(135±14)vs.(168±9)at 2 h,(174±10)vs.(211±12)at 4 h,(192±10)vs.(253±13)at 24 h;BUN(mmol/L):(10.5±1.0)vs.(12.3±1.0)at 1 h,(12.2±1.2)vs.(15.3±0.9)at 2 h,(13.6±1.3)vs.(18.3±1.2)at 4 h,(15.4±1.4)vs.(21.5±1.4)at 24 h;IFAB
作者 卢晓驰 兰频 潘群婕 刘英 徐杰丰 周光居 张茂 Lu Xiaochi;Lan Pin;Pan Qunjie;Liu Ying;Xu Jiefeng;Zhou Guangju;Zhang Mao(Department of Emergency Medicine,Second Affiliated Hospital,Zhejiang University School of Medicine,Zhejiang Key Laboratory for Diagnosis and Treatment of Severe Trauma and Burn,Zhejiang Critical and Critical Care Clinical Medical Research Center,Hangzhou 310009,China;Department of Emergency Medicine,Lishui Muncipal Central Hospital,Lishui 323000,China;Department of Emergency Medicine,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)
出处 《中华急诊医学杂志》 CAS CSCD 北大核心 2023年第3期339-345,共7页 Chinese Journal of Emergency Medicine
基金 国家自然科学基金(82072126) 浙江省重点研发计划项目(2021C03073、2021C03036) 丽水市科技计划项目(2022GYX36、2023GYX24)。
关键词 心脏骤停 心肺复苏 急性肾损伤 肠黏膜损伤 丁酸钠 自噬 凋亡 Cardiac arrest Cardiopulmonary resuscitation Acute kidney injury Intestinal mucous injury Sodium butyrate Autophagy Apoptosis
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