摘要
目的研究在免疫性肝损伤大鼠模型中,抑制核转录因子κB (nuclear factor kappa B,NF-κB)的活化对细胞色素P450总含量、亚型1A2(CYP1A2)表达、代谢活力的影响。方法采用尾静脉注射卡介苗(BCG)125 mg·kg^(-1) 14 d制备免疫性肝损伤大鼠模型。采用双光束紫外分光光度法测定肝匀浆中CYP450总含量;肝脏组织HE染色法和测定血清中ALT、AST水平,检测大鼠肝损伤情况; Western blot法检测大鼠肝组织中CYP1A2蛋白表达; HPLC法检测CYP1A2的探针药物茶碱的血浆药物浓度经时变化,从而反映CYP1A2的代谢活力。结果大鼠尾静脉注射BCG 14 d后,可引起肝组织炎性细胞浸润,肝重、脾重增加,血清转氨酶ALT及AST水平明显升高,CYP450总含量降低,CYP1A2表达和代谢活力明显降低。采用吡咯烷二硫氨基甲酸(PDTC)抑制NF-κB活化,可缓解CYP450总含量的降低,减缓CYP1A2蛋白表达和代谢活力的下调。结论免疫损伤刺激明显下调CYP1A2,钝化NF-κB活化可明显抑制免疫性肝损伤大鼠肝组织中CYP1A2的下调,NF-κB可能参与CYP1A2下调机制。
Aim To determine the function of nuclear factor-κB(NF-κB)in immunological liver injury of rat model and its effect on CYP1A2 expression,content and metabolic activity.Methods The immunological liver injury rat model was prepared by injection of Bacillus Calmette Guérin(BCG)125 mg·kg^-1 for 14 days.The hepatic tissue injury was revealed by hematoxylin and eosin(HE)method and serum concentration of alanine aminotransferase(ALT),aspartate aminotransferase(AST)respectively.CYP450 total content in hepatic homogenate was determined by spectrophotography.The expression of CYP1A2 protein was detected by Western blot.The enzyme kinetics of CYP1A2 probe drug theophylline was evaluated by high-performance liquid chromatography(HPLC)assay.Results BCG-pretreatment significantly increased the weight of liver and spleen,serum levels of ALT and AST,and decreased CYP1A2 expression,content and metabolic activity.The administration of ammonium pyrrolidine dithiocarbamate(PDTC)reversed the above hepatic injury stimulated by BCG in vivo.Moreover,PDTC dose-dependently inhibited the down-regulation of CYP1A2.Conclusions Passivation of NF-κB can inhibit the down-regulation of CYP1A2 in liver tissues of immunological liver injury;NF-κB may be involved in CYP1A2 down-regulation.
作者
林琴
贾金雪
王涛
李晓霞
刘凤婷
薛永志
LIN Qin;JIA Jin-xue;WANG Tao;LI Xiao-xia;LIU Feng-ting;XUE Yong-zhi(Institute of Pharmacolinetics and Liver Molecular Pharmacology,Dept of Pharmacology,Baotou Medical College,Baotou 014060,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2018年第11期1605-1609,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81460567)
内蒙古自然科学基金资助项目(No 2009MS1104,2014MS0813)
内蒙古教育厅资助项目(No NJ03148,NJZY13244)。
