中华消化杂志
中華消化雜誌
중화소화잡지
Chinese Journal of Digestion
2008年
11期
733-736
,共4页
王春妍%范玉强%迟宝荣%曹武奎
王春妍%範玉彊%遲寶榮%曹武奎
왕춘연%범옥강%지보영%조무규
肝脏疾病%核因子-κB%疾病模型,动物
肝髒疾病%覈因子-κB%疾病模型,動物
간장질병%핵인자-κB%질병모형,동물
Liver disease%Nuclear factor-kappa B%Disease model,animal
目的 探讨核因子-κB(NF-κB)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1 h腹腔内注射PDTC 100 mg/kg.然后,三组大鼠分别于6、24、48 h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-κB活性.结果 ①TAA造模组造模后6、24和48 h NF-κB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-κB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-α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48 h较正常组增加(P值均＜0.01).④TAA造模组各时间点ICAM-lmRNA表达较正常组显著升高(P值均＜0.01).PDTC预处理组各时间点ICAM-lmRNA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造模组同时间点明显减轻.结论 NF-κB在TAA所致急性肝损伤中通过促进TNF-α、IL-6及ICAM-1的表达而发挥作用,加重肝损伤.
目的 探討覈因子-κB(NF-κB)在硫代乙酰胺(TAA)所緻急性肝損傷中的作用及機製.方法 雄性Wistar大鼠78隻分為正常組18隻,TAA造模組30隻及脯氨痠二硫代氨基甲痠酯(PDTC)預處理組30隻.PDTC預處理組于建立急性肝損傷模型前1 h腹腔內註射PDTC 100 mg/kg.然後,三組大鼠分彆于6、24、48 h處死,TAA造模組及PDTC預處理組每時間點各取10隻大鼠,正常組每時間點各取6隻大鼠.測定大鼠血漿內毒素、腫瘤壞死因子-α(TNF-α)、白細胞介素-6(IL-6)水平,RT-PCR方法檢測肝髒組織細胞間粘附因子-1(ICAM-1)mRNA錶達,取肝髒行病理學及免疫組化檢測NF-κB活性.結果 ①TAA造模組造模後6、24和48 h NF-κB細胞暘性率分彆為(87.11±8.23)%、(78.55±6.82)%和(74.27±6.26)%,與正常組相比差異均有統計學意義[(4.64±1.82)%、(4.55±1.67)%和(4.91±2.12)%,P值均＜0.01].PDTC預處理組各時間點NF-κB細胞暘性率分彆為(31.88±4.14)%、(27.58±3.44)%和(26.67±3.88)%,與TAA造模組相比暘性率明顯降低(P值均＜0.01).②TAA造模組各時間點血漿內毒素和TNF-α水平含量明顯較正常組升高(P值均＜0.01),而PDTC預處理組則較TAA造模組降低(P值均＜0.01),但較正常組有所增高(P值均＜0.01).③TAA造模組各時間點IL-6水平較正常組顯著升高(P值均＜0.01).PDTC預處理組各時間點IL-6水平較TAA造模組明顯降低(P值分彆＜0.05和0.01);24和48 h較正常組增加(P值均＜0.01).④TAA造模組各時間點ICAM-lmRNA錶達較正常組顯著升高(P值均＜0.01).PDTC預處理組各時間點ICAM-lmRNA錶達較TAA造模組明顯降低(P值均＜0.01).但較正常組增高(P值均＜0.01).⑤TAA造模組各時間段可見肝組織壞死,PDTC預處理組各時間段肝組織病理改變較TAA造模組同時間點明顯減輕.結論 NF-κB在TAA所緻急性肝損傷中通過促進TNF-α、IL-6及ICAM-1的錶達而髮揮作用,加重肝損傷.
목적 탐토핵인자-κB(NF-κB)재류대을선알(TAA)소치급성간손상중적작용급궤제.방법 웅성Wistar대서78지분위정상조18지,TAA조모조30지급포안산이류대안기갑산지(PDTC)예처리조30지.PDTC예처리조우건립급성간손상모형전1 h복강내주사PDTC 100 mg/kg.연후,삼조대서분별우6、24、48 h처사,TAA조모조급PDTC예처리조매시간점각취10지대서,정상조매시간점각취6지대서.측정대서혈장내독소、종류배사인자-α(TNF-α)、백세포개소-6(IL-6)수평,RT-PCR방법검측간장조직세포간점부인자-1(ICAM-1)mRNA표체,취간장행병이학급면역조화검측NF-κB활성.결과 ①TAA조모조조모후6、24화48 h NF-κB세포양성솔분별위(87.11±8.23)%、(78.55±6.82)%화(74.27±6.26)%,여정상조상비차이균유통계학의의[(4.64±1.82)%、(4.55±1.67)%화(4.91±2.12)%,P치균＜0.01].PDTC예처리조각시간점NF-κB세포양성솔분별위(31.88±4.14)%、(27.58±3.44)%화(26.67±3.88)%,여TAA조모조상비양성솔명현강저(P치균＜0.01).②TAA조모조각시간점혈장내독소화TNF-α수평함량명현교정상조승고(P치균＜0.01),이PDTC예처리조칙교TAA조모조강저(P치균＜0.01),단교정상조유소증고(P치균＜0.01).③TAA조모조각시간점IL-6수평교정상조현저승고(P치균＜0.01).PDTC예처리조각시간점IL-6수평교TAA조모조명현강저(P치분별＜0.05화0.01);24화48 h교정상조증가(P치균＜0.01).④TAA조모조각시간점ICAM-lmRNA표체교정상조현저승고(P치균＜0.01).PDTC예처리조각시간점ICAM-lmRNA표체교TAA조모조명현강저(P치균＜0.01).단교정상조증고(P치균＜0.01).⑤TAA조모조각시간단가견간조직배사,PDTC예처리조각시간단간조직병리개변교TAA조모조동시간점명현감경.결론 NF-κB재TAA소치급성간손상중통과촉진TNF-α、IL-6급ICAM-1적표체이발휘작용,가중간손상.
Objective To investigate the mechanism of nuclear factor-kappa B(NF-κB)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 rag/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-κB activity was 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 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＜0.0 1).but lower than those in TAA with ticrmal 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＜group(P＜0.01).The expression of ICAM-1 in PDTC pretreated group was higher than that in immunohistochemical examination showed that liver necrosis was folund in TAA group and PDTC pretreated group.Conclusion The Nuclear factor-κB may aggravate the injury of liver by promoting expressions of TNF-α,IL-6 and ICAM-1.
