肝移植后环孢素对核因子κB活性和γ干扰素基因转录表达的影响  

Ciclosporin down-regulates interferon-γ gene transcription via its inhibition of nuclear factor κB activity after liver transplantation

作　　者：贾长库[1] 郑树森[1] 施邵华[1] 章爱斌[1] 谢海洋[1] 

机构地区：[1]浙江大学医学院附属第一医院肝胆胰外科,杭州310003

出　　处：《中华外科杂志》2004年第17期1052-1055,共4页Chinese Journal of Surgery

基　　金：浙江省科技厅资助项目 (0 110 96)

摘　　要：目的　研究肝移植后环孢素对核因子κB (NF κB)的活性与γ干扰素 (IFN γ)基因转录表达的影响。方法　采用大鼠原位肝移植模型 ,用凝胶电泳迁移率和逆转录聚合酶链反应 (RT PCR)的方法 ,分别测定移植后环孢素处理前后脾细胞NF κB的活性及移植肝中IFN γmRNA的表达。结果　大鼠原位肝移植后 ,在Wistar Wistar同基因移植组中 ,仅在 5d和 7d时间段检测到较低的NF κB活性 ,各时间段肝组织中仅有较弱的IFN γmRNA表达 ;SD Wistar急性排斥组中 ,各时间段均检测到明显的NF κB活性 ,肝组织的IFN γmRNA也处于高表达状态 ;SD Wistar急性排斥加用环孢素治疗后 ,显著的抑制了NF κB的活性 (P =0 0 0 1) ,肝组织IFN γmRNA的表达也同样受到显著抑制 (P <0 0 0 1) ,两者具有良好的相关性 (r =0 815 ,P <0 0 1)。结论　原位肝移植后IFN γmRNA表达的变化 ,至少部分是由于NF κB活性改变所致 ,环孢素可以降低NF κB活性 ,进而抑制IFN γmRNA表达 ;阻断NFObjective To investigate the relation between the activity of nuclear factor κB (NF κB) and the expression of interferon (IFN) γ gene transcription with or without ciclosporin treatment after liver transplantation Methods Orthotopic liver transplantation was performed in this study GroupⅠ:syngeneic control (Wistar to Wistar); GroupⅡ:acute rejection (SD to Wistar ); Group Ⅲ:acute rejection treated with ciclosporin by intramuscular route (SD to Wistar+ciclosporin) Electrophoretic mobility shift assay and reverse trascriptase polymerase chain reaction were used to analyze NF κB activity of splenocytes and IFN γ gene transcription expression of grafted liver with or without ciclosporin treatment after liver transplantation Histopathological examination was also used in this study Results Low NF κB activity was only detected at day 5 and day 7 in Wistar to Wistar group after transplantation, meanwhile low IFN γmRNA expression was detected at any time in this group In contrast,high NF κB activity was detected in SD to Wistar group and high level IFN γmRNA expression was detected at all time points in this group The activity of NF κB and IFN γmRNA expression were significantly inhibited in SD to Wistar+ciclosporin group which was significantly lower than that of SD to Wistar group( P <0 001) A good correlation was found between activity of NF κB and IFN γ mRNA expression in this study( r =0 815, P <0 01) Conclusions The change of expression IFN γ mRNA is at least partially due to the activity change of NF κB after orthotopic liver transplantation CsA down regulates NF κB activity and further inhibit IFN γ gene transcription

关 键 词：NF—κB 环孢素 IFN-γ 原位肝移植 表达 活性 Γ干扰素 RNA 基因转录 凝胶电泳 

分 类 号：R657.3[医药卫生—外科学] R512[医药卫生—临床医学]