他克莫司对移植免疫反应中核因子κB活性和淋巴细胞趋化因子表达的影响  

Tacrolimus inhibits NF-κB activity and lymphotactin gene expression after heart transplantation in mouse

作　　者：万云乐[1] 吴丽花[2] 赵志成[2] 贾长库[2] 谢海洋[2] 郑树森[2] 

机构地区：[1]中山大学附属第二医院肝胆胰外科,广州510120 [2]浙江大学医学院附属第一医院肝胆胰外科卫生部多器官联合移植研究重点实验室

出　　处：《中华移植杂志（电子版）》2010年第1期30-33,共4页Chinese Journal of Transplantation(Electronic Edition)

基　　金：国家重点基础研究发展计划(973计划)资助项目(2009CB522403)

摘　　要：目的研究他克莫司(FK506)对移植免疫反应中细胞核因子κB(NF-κB)活性和淋巴细胞趋化因子(Lptn)表达的影响。方法应用小鼠同种心脏移植急性排斥反应模型,分为BALB/c-BALB/c同基因对照组、C57BL/6-BALB/c异基因对照组、C57BL/6-BALB/c移植+FK506处理组。RT-PCR检测移植心组织内Lptn mRNA的表达,凝胶电泳迁移率和ELISA分别检测心脏移植小鼠脾细胞NF-κB的活性和活化T细胞核因子(NFAT)c1活性。结果同基因移植组各时间点移植心内无Lptn mRNA表达;异基因移植组和FK506处理组移植后第1天和第3天均无Lptn mRNA表达,而第5天和第7天均可检测到Lptn mRNA阳性表达,但FK506组Lptn mRNA表达受抑制。治疗剂量的FK506可以明显抑制脾细胞NF-κB和NFATc1的活性,但FK506处理组心脏移植后第5、7天脾细胞NF-κB的活性仍明显高于同基因移植组。NF-κB活性与Lptn基因转录水平呈正相关关系(r=0.775,P=0.000)。结论 FK506除了通过抑制NFATc1活性途径调控部分Lptn mRNA的表达,还可通过抑制NF-κB途径参与Lptn mRNA表达的调控。Objective To investigate the effect of tacrolimus（FKA06） on NF-κB activity and lymphotactin （Lptn） gene transcription in murine cardiac transplantation. Methods A fully major histocompatibility complex incompatible C57 BL/6 （ H- 2b） - to- BALB/c （ H- 2d ） murine cardiac transplantation model was used for in vivo studies. All mice were randomly divided into BALB/c-to-BALB/c isograft group, C57BL/6-to-BALB/e allograft group, and allograft ＋ FK506 group. Histopathological changes of graft specimens were examined at indicated time. Reverse transcription PCR was used to determine the mRNA expression of Lptn in cardiac grafts. NF-κB （p65/p50） and NFATcl activity of splenocytes after transplantation was assessed by the enzyme-linked immunoabsorbent assay. NF-κB activity was also identified by the electrophoretic mobility shift assay. Results Lptn mRNA was undetectable in cardiac isografts. Lptn mRNA transcription which was undetectable on day 1 and day 3 was upregulated in acutely rejecting cardiac allografis on postoperative day 5 and clay 7, and this upregulation was partially inhibited by FKS06. NFATc1 activity in splenocytes which was markedly upregulated during acute rejection was completely inhibited by FKS06 given intraperitoneally at a close of 1 mg · kg^-1· d^-1, while NF-κB （P65/ P50）activity on day postoperative 5 and day 7 was still higher than that in the isografts. A positive correlation was found between NF-κB （P65/P50）activity and Lptn mRNA expression（ r = 0.775, P = 0. 000）.Conclusion FK506 may play a role in the regulation of Lptn mRNA expression by completely inhibiting NFATcl activity and partially blocking NF- κ（P65/P50） activity.

关 键 词：小鼠 心脏移植 移植物排斥 他克莫司 核因子κB 淋巴细胞趋化因子 

分 类 号：R96[医药卫生—药理学]