核因子-kB在硫代乙酰胺所致急性肝损伤中的作用及机制研究  

The mechanism of nuclear factor-kappa B in thioactamide induced acute hepatic injury

作　　者：王春妍[1] 范玉强[1] 迟宝荣[2] 曹武奎[1] 

机构地区：[1]天津市传染病医院重肝科 天津市肝病研究所,300192 [2]吉林大学第一医院消化科

出　　处：《中华消化杂志》2008年第11期733-736,共4页Chinese Journal of Digestion

摘　　要：目的探讨核因子-kB（NF-kB）在硫代乙酰胺（TAA）所致急性肝损伤中的作用及机制。方法雄性Wistar大鼠78只分为正常组18只，TAA造模组30只及脯氨酸二硫代氨基甲酸酯（PDTC）预处理组30只。PDTC预处理组于建立急性肝损伤模型前1h腹腔内注射PDTC100mg／kg。然后，三组大鼠分别于6、24、48h处死，TAA造模组及PDTC预处理组每时间点各取10只大鼠，正常组每时间点各取6只大鼠。测定大鼠血浆内毒素、肿瘤坏死因子-α（TNF—α）、白细胞介素-6（IL-6）水平，RT—PCR方法检测肝脏组织细胞间粘附因子-1（ICAM-1）mRNA表达，取肝脏行病理学及免疫组化检测NF—kB活性。结果①TAA造模组造模后6、24和48hNF-kB细胞阳性率分别为（87．11±8．23）%、（78．55±6．82）％和（74．27±6．26）%，与正常组相比差异均有统计学意义[（4．64±1．82）％、（4．55±1．67）％和（4．91±2．12）％，P值均〈0．01]。PDTC预处理组各时间点NF-kB细胞阳性率分别为（31．88±4．14）％、（27．58±3．44）％和（26．67±3．88）％，与TAA造模组相比阳性率明显降低（P值均〈0．01）。②TAA造模组各时间点血浆内毒素和TNF-a水平含量明显较正常组升高（P值均〈0．01），而PDTC预处理组则较TAA造模组降低（P值均〈0．01），但较正常组有所增高（P值均〈0．01）。③TAA造模组各时间点IL-6水平较正常组显著升高（P值均〈0．01）。PDTC预处理组各时间点IL-6水平较TAA造模组明显降低（P值分别〈0．05和0．01）；24和48h较正常组增加（P值均〈0．01）。④TAA造模组各时间点ICAM—1mRNA表达较正常组显著升高（P值均〈0．01）。PDTC预处理组各时间点KAM—1mRNA表达较TAA造模组明显降低（P值均〈0．01），但较正常组增高（P值均〈0．01）。⑤TAA造模组各时间段可见肝组织坏死，PDTC预处理组各时间段肝组织病理改变较TAA造模组同时�Objective To investigate the mechanism of nuclear factor-kappa B （NF-kB） in thioactamide （TAA） induced acute hepatic injury. Methods Seventy-eight Wistar rats were randomly divided into normal group （n = 18）, TAA model group （n = 30）and pyrrolidine dithiocarbamate （PDTC） pretreated group（n=30）. The rats in PDTC group were received 100 mg/kg of PDTC 1 h before induction of the model. Every 10 rats in TAA group and PDTC pretreated group and 6 rats in normal group were sacrificed at 6, 24, 48 hour after induction of the model to mesure levels of endotoxin, tumor necrosis factor（TNF）-α and interleukin（IL）-6. The expression of the intercellular adhesion molecular （ICAM）-1 in hepatic tissue was tested using RT-PCR and the NF-kB activity was examined pathologically and immunohistochemieally. Results ① The activities of NF-kB at 6,24 and 48 hour were higher in TAA group[（87.11 ± 8.23）%, （78.55 ± 6.82）% and （74.27 ± 6.26）%, respectively] than those in normal group [（4.64±1.82）% ,（4.55±1.67）% and（4.91±2.12）% ,all P value〈0.01]. ② The serum concentration of endotoxin and TNF-α in TAA group were increased in comparison with normal group （P〈0.01）. The serum concentration of endotoxin and TNF-α in PDTC pretreated group were higher than those in normal group （P〈0.01）, but lower than those in TAA group （P〈0.01）. ③ The serum concentration of IL 6 in TAA group was increased in comparison with normal group （P〈0.01）. The serum concentration of IL 6 in PDTC pretreated group was higher at 24 and 48 hour than those in normal group （P〈0.01） , but lower than thoes in TAA group （P〈 0.01）. ④ The expression of ICAM-1 in the hepatic tissue was increased in comparison with normal group （P〈0.01）. The expression of ICAM-t in PDTC pretreated group was higher than that in normal group （P 〈 0.01 ）, but lower than that in TAA group （P 〈 0.01 ）. ⑤ The immunohistochemical examination showed that liver necrosis was fou

关 键 词：肝脏疾病 核因子-KB 疾病模型 动物 

分 类 号：R686[医药卫生—骨科学]