JNK抑制剂对仔猪肝细胞药物性损伤的缓解作用及其机理  

Mitigating Effect and Mechanism of JNK Inhibitor on Drug-induced Injury of Piglet Hepatocytes

作　　者：王奔 袁帅 郑怡 张宏玲 WANG Ben;YUAN Shuai;ZHENG Yi;ZHANG Hongling(College of Animal Science,Jilin Agricultural Science and Technology College,Jilin 132101,China)

机构地区：[1]吉林农业科技学院动物科技学院,吉林132101

出　　处：《中国畜牧兽医》2022年第5期1888-1894,共7页China Animal Husbandry & Veterinary Medicine

基　　金：吉林市科技创新发展计划项目(201831783)。

摘　　要：【目的】研究c-Jun氨基末端激酶(JNK)抑制剂SP600125对仔猪原代肝细胞药物性损伤的缓解作用及机理。【方法】通过二步灌流法获得仔猪原代肝细胞,将肝细胞分为对照组(C)、JNK抑制剂组(SP)、模型组(M)和治疗组(T),每组6个重复。对照组细胞不添加药物,SP组用2μmol/L SP600125处理细胞,M组用80μg/mL脂多糖(LPS)+20μg/mL恩诺沙星(ENR)处理细胞,T组用80μg/mL LPS+20μg/mL ENR+2μmol/L SP600125处理细胞,处理12 h后,收集上清测定谷丙转氨酶(ALT)和谷草转氨酶(AST)活性,收集细胞测定谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、超氧化物歧化酶(superoxide dismutase,SOD)活性、丙二醛(malondialdehyde,MDA)含量及肝细胞核因子-1(hepatocyte nuclear factor 1,HNF-1)和谷胱甘肽-S-转移酶A1(glutathione S-transferase alpha 1,GSTA1)mRNA的相对表达量。【结果】与对照组相比,M组肝细胞培养液上清中ALT和AST活性均显著升高(P<0.05),M组肝细胞中GSH-Px和SOD活性、HNF-1和GSTA1 mRNA的相对表达量均极显著降低(P<0.01),MDA含量极显著提高(P<0.01);与M组相比,T组肝细胞培养液上清中ALT、AST的活性均显著下降(P<0.05),T组肝细胞中GSH-Px和SOD活性、HNF-1和GSTA1 mRNA的相对表达量均显著提高(P<0.05),MDA含量显著降低(P<0.05)。【结论】JNK抑制剂SP600125可通过调控细胞的抗氧化能力及HNF-1和GSTA1的表达缓解由LPS/ENR导致的仔猪原代肝细胞的药物性损伤。【Objective】The aim of this study was to investigate the alleviating effect and mechanism of c-Jun N-terminal kinase(JNK)inhibitor SP600125 on the pharmacological damage of primary hepatocytes in piglets.【Method】Piglet primary hepatocytes were obtained by two-step perfusion method,and the hepatocytes were divided into control group(C),JNK inhibitor group(SP),model group(M)and treatment group(T),with 6 replicates in each group.The cells in control group were not added with drugs,SP group cells were treated with 2μmol/L SP600125,M group cells were treated with 80μg/mL lipopolysaccharide(LPS)+20μg/mL enrofloxacin(ENR),T group cells were treated with 80μg/mL LPS+20μg/mL ENR+2μmol/L SP600125.After treatment for 12 h,supernatants were collected to determine alanine transaminase(ALT)and glutamic oxalacetic transaminase(AST)activities,and cells were collected to determine the activities of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),and the content of malondialdehyde(MDA)and the relative expression of hepatocyte nuclear factor 1(HNF-1)and glutathione S-transferase alpha 1(GSTA1)mRNA.【Result】Compared with control group,the activities of ALT and AST in hepatocyte culture medium were significantly increased in M group(P<0.05),the activities of GSH-Px,SOD and the relative expression of HNF-1,GSTA1 mRNA in hepatocytes were extremely significantly decreased in M group(P<0.01),and MDA content in hepatocytes was extremely significantly increased(P<0.01).Compared with M group,the activities of ALT and AST in hepatocyte culture medium were significantly decreased in T group(P<0.05),the activities of GSH-Px,SOD and the relative expression of HNF-1,GSTA1 mRNA in hepatocytes were significantly increased in T group(P<0.05),and MDA content was significantly decreased(P<0.05).【Conclusion】JNK inhibitor SP600125 could alleviate the drug-induced injury of piglet primary hepatocytes caused by LPS/ENR by regulating the antioxidant capacity and the expression of HNF-1 and GSTA1 of cells.

关 键 词：原代肝细胞 药物性损伤 JNK抑制剂 抗氧化 

分 类 号：S852.21[农业科学—基础兽医学]