远端缺血预处理对对乙酰氨基酚诱导急性肝损伤小鼠氧化应激和炎症反应的保护作用  

Protective effects of remote ischemic preconditioning on acetaminophen-induced oxidative stress and inflammation in mice with acute liver injury

作　　者：郑伟[1] 党珊[2] 张智勇[1] 万永[3] 刘司南[3] 常虎林[1] ZHENG Wei;DANG Shan;ZHANG Zhi-yong;WAN Yong;LIU Si-nan;CHANG Hu-lin(Department of Hepatobiliary Surgery,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Geriatric Gastroenterology,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Hepatobiliary Surgery,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]陕西省人民医院肝胆外科,陕西西安710068 [2]陕西省人民医院老年消化科,陕西西安710068 [3]西安交通大学第一附属医院肝胆外科,陕西西安710061

出　　处：《肝胆胰外科杂志》2021年第12期741-746,共6页Journal of Hepatopancreatobiliary Surgery

基　　金：陕西省人民医院科技项目(2020YXM-16);陕西省科技计划项目-社会发展领域(2021SF-236)。

摘　　要：目的探讨远端缺血预处理(remote ischemic preconditioning,RIPC)对对乙酰氨基酚(acetaminophen,APAP)诱导的急性肝损伤小鼠的保护机制。方法采用腹腔注射APAP溶液诱导小鼠急性肝损伤模型。按随机数字表法将6~8周龄、体质量22~25 g的C57BL/6雄性小鼠分为空白对照组(C组)、假手术组(S组)、肝损伤组(A组)及远端缺血预处理组(R组),每组10只。处理16 h后取小鼠血标本及肝脏组织,检测各组血清谷丙转氨酶(ALT)与谷草转氨酶(AST)活性、血清肿瘤坏死因子-α(TNF-α)与白介素-6(IL-6)水平,检测肝组织活性氧(ROS)、丙二醛(MDA)含量以及超氧化物歧化酶(SOD)与谷胱甘肽酶(GSH)活性,检测肝组织中Kelch样环氧氯丙烷相关蛋白-1(Keap1)、核因子E2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)表达的变化。组间比较采用单因素方差分析。结果(1)肝功能指标:与C组和S组的ALT、AST比较,A组ALT[(5643.20±688.21)U/L]和AST[(4479.10±834.46)U/L]水平明显升高,差异有统计学意义(均P<0.05);R组ALT[(3730.12±599.33)U/L]和AST[(3592.52±646.13)U/L]水平明显低于A组,差异有统计学意义(均P<0.05)。(2)炎症因子水平:与C组和S组血清TNF-α、IL-6比较,A组血清TNF-α[(337.75±48.57)pg/mL]和IL-6[(938.03±160.90)pg/mL]水平明显升高,差异有统计学意义(均P<0.05);R组血清TNF-α[(235.55±65.77)pg/mL]和IL-6[(713.48±87.78)pg/mL]水平明显低于A组,差异有统计学意义(均P<0.05)。(3)氧化应激程度:与C组和S组对比,A组ROS产生较多,肝内MDA[(13.20±1.94)nmol/mg protein]含量增高,GSH[(7.13±0.89)mg/g protein]和SOD[(8.15±0.65)U/mg protein]活性降低,差异有统计学意义(均P<0.05);与A组相比,R组ROS产生减少,肝内MDA[(8.50±0.82)nmol/mg protein]活性降低,GSH[(10.36±0.96)mg/g protein]和SOD[(11.14±1.61)U/mg protein]活性则明显升高,差异有统计学意义(均P<0.05)。(4)与C组和S组对比,A组Keap1、Nrf2和HO-1的蛋白相对表达强度降低,而R组显著改善(P<0.05)。结�Objective To investigate the protective effect of remote ischemic preconditioning(RIPC)against acetaminophen(APAP)-induced acute liver injury in mice and the possible mechanisms.Methods Mouse models of liver injury were obtained by intraperitoneal injection with APAP.Male C57BL/6 mice were randomly divided into blank control group(C group),sham operation group(S group),liver injury model group(A group)and RIPC+APAP group(R group),10 mouse in each group.Blood samples and liver tissues were collected at 16 h after APAP modeling,to determine the alanine transaminase(ALT)and aspartate transaminase(AST);tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels;reactive oxygen(ROS)malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione(GSH);the expression of epoxy chloropropane Kelch sample related protein-1(Keap1),nuclear factor erythroid-2 related factor(Nrf2)and Heme oxygenase-1(HO-1).Results(1)Liver function:compared with C and S group,the levels of ALT[(5643.20±688.21)U/L]and AST[(4479.10±834.46)U/L]in A group were significantly higher(P<0.05),while the levels of ALT[(3730.12±599.33)U/L]and AST[(3592.52±646.13)U/L]in R group were significantly lower than those in A group(P<0.05).(2)Serum levels of inflammatory factor:compared with C and S group,the levels of TNF-a[(337.75±48.57)pg/mL]and IL-6[(938.03±160.90)pg/mL]in A group were significantly higher(P<0.05),while the levels of TNF-a[(235.55±65.77)pg/mL and IL-6(713.48±87.78)pg/mL]in R group were significantly lower than those in A group(P<0.05).(3)Degree of oxidative stress:compared with C and S group,ROS was less,the levels of MDA[(13.20±1.94)nmol/mg protein]in A group were significantly higher(P<0.05),and the levels of GSH[(7.13±0.89)mg/g protein]and SOD[(8.15±0.65)U/mg protein]in A group were significantly lower(P<0.05);meanwhile,ROS was more,the levels of MDA[(8.50±0.82)nmol/mg protein]in R group were significantly lower,and the levels of GSH[(10.36±0.96)mg/g protein]and SOD[(11.14±1.61)U/mg protein]were significantly higher than those

关 键 词：远端缺血预处理 对乙酰氨基酚 急性肝损伤 炎症 氧化应激 小鼠 

分 类 号：R333.4[医药卫生—人体生理学] R575[医药卫生—基础医学]