人工远端肢体缺血再灌注对APAP诱导小鼠肝损伤的保护作用研究  

Effect of Artificial Remote Ischemia-Reperfusion Conditioning on Acetaminophen-Induced Acute Liver Injury in Mice and Its Possible Mechanism

作　　者：郑伟[1] 宋晓雪[1] 严翔 张智勇[1] 常虎林[1] ZHENG Wei;SONG Xiao-xue;YAN Xiang;ZHANG Zhi-yong;CHANG Hu-lin(Department of Hepatobiliary Surgery,Shaanxi Provincial People’s Hospital,Xi’an 710068,China)

机构地区：[1]陕西省人民医院肝胆外科,西安710068

出　　处：《现代检验医学杂志》2021年第4期60-63,110,共5页Journal of Modern Laboratory Medicine

基　　金：西安市科技计划医学项目(20YXYJ0010)。

摘　　要：目的研究人工远端肢体缺血再灌注预处理(R-IPC)和缺血再灌注后处理(R-IPOST)对对乙酰氨基酚(APAP)诱导小鼠肝损伤的保护作用。方法按随机数字表法将实验小鼠分为5组:正常对照组(不做任何处理)、假手术组(缺血再灌注处理前后腹腔注射1ml生理盐水)、APAP组(腹腔注射1ml APAP溶液)、R-IPC+APAP组(缺血再灌注预处理后腹腔注射1ml APAP溶液)、R-IPOST+APAP组(腹腔注射1ml APAP溶液后实施缺血再灌注后处理)。观察各组肝脏病理形态变化;检测各组血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性、肿瘤坏死因子-a(TNF-a)水平、白细胞介素-6(IL-6)水平;检测各组肝组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽酶(GSH)的水平和比较各指标组间差异。结果光镜下R-IPC+APAP组和R-IPOST+APAP组肝小叶结构破坏程度及炎性细胞浸润程度较APAP组均明显减轻。R-IPC+APAP组血清ALT,AST,TNF-a,IL-6和肝匀浆MDA含量均明显低于APAP组[(3742±519.7 U/L,3471±631.4U/L,264.8±70.4pg/ml,738.7±71.0 pg/ml,8.9±1.2nmol/mg.prot)vs(5564±621.7U/L,4647±813.9U/L,351.7±52.3pg/ml,929.7±140.6pg/ml,13.1±1.7nmol/mg.prot)],差异均有统计学意义(t=3.400~7.032,均P<0.05);R-IPC+APAP组肝匀浆SOD活性明显高于APAP组(11.0±1.9U/mg.prot vs 8.6±1.1U/mg.prot),差异有统计学意义(t=3.043,P<0.05);R-IPOST+APAP组血清ALT,AST,TNF-a,IL-6和肝匀浆MDA含量均明显低于APAP组[(3410±588.6 U/L,3546±499.5U/L,256.6±48.1pg/ml,775.4±98.4pg/ml,9.3±1.9nmol/mg.prot)vs(5564±621.7U/L,4647±813.9U/L,351.7±52.3pg/ml,929.7±140.6pg/ml,13.1±1.7nmol/mg.prot)],差异均有统计学意义(t=2.196~4.981,均P<0.05);R-IPOST+APAP组肝匀浆GSH活性明显高于APAP组(10.3±1.2U/mg.prot vs 7.9±0.6U/mg.prot),差异有统计学意义(t=3.702,P<0.05)。结论R-IPC和R-IPOST能降低APAP诱导的药物性肝损伤氧化应激和炎症反应程度,对肝功能具有保护作用。Objective To study the effect of artificial remote ischemia-reperfusion preconditioning(R-IPC)and remote ischemia-reperfusion postconditioning(R-IPOST)on acetaminophen(APAP)-induced liver injury.Methods Five groups in this study:control group(mice remained untreated),sham operation group(mice subjected to remote ischemic conditioning manipulation and followed by an intraperitoneal injection of saline),APAP group(mice received intraperitoneal injection of 1 ml APAP),R-IPC+APAP group(mice subjected to R-IPC followed 5 min later by an injection of APAP),R-IPOST+APAP group(mice subjected to an injection of APAP followed 5 min later by R-IPOST).The pathological changes of liver were observed,Serum aminotransferase,alanine aminotransferase(ALT),Serum transaninase(AST)were detected.Malondialdehyde(MDA)content,superoxide dismutase(SOD)and tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels,glutathione s-transferase(GSH),levels in liver tissue of each group were detected.Results The histopathological abnormalities were attenuated in R-IPC+APAP and R-IPOST+APAP group.The level of ALT,AST,TNF-a,IL-6 and MDA in R-IPC+APAP group were significantly lower than in APAP group[(3742±519.7 U/L,3471±631.4U/L,264.8±70.4pg/ml,738.7±71.0pg/ml,8.9±1.2nmol/mg.prot)vs(5564±621.7U/L,4647±813.9U/L,351.7±52.3pg/ml,929.7±140.6pg/ml,13.1±1.7nmol/mg.prot)],the difference were statistically significant(t=3.400~7.032,all P<0.05).The SOD level was increased in R-IPC+APAP group than in APAP group(11.0±1.9U/mg.prot vs 8.6±1.1U/mg.prot),the diffenence was statistically significant(t=3.043,P<0.05).The level of ALT,AST,TNF-a,IL-6 and MDA in R-IPOST+APAP group were significantly lower than in APAP group[(3410±588.6 U/L,3546±499.5U/L,256.6±48.1pg/ml,775.4±98.4pg/ml,9.3±1.9nmol/mg.prot)vs(5564±621.7U/L,4647±813.9U/L,351.7±52.3pg/ml,929.7±140.6pg/ml,13.1±1.7nmol/mg.prot)],the difference were statistically significant(t=2.196~4.981,all P<0.05).The GSH level was higher in R-IPOST+APAP group than in APAP group(10.3±1.2U/mg.pro

关 键 词：远端肢体缺血再灌注预处理 远端肢体缺血再灌注后处理 对乙酰氨基酚 肝损伤 小鼠 

分 类 号：R-332[医药卫生]