环孢菌素A抑制小鼠同种心脏移植急性排斥反应中Lymphotactin表达的研究  

Lymphotactin gene transcription is inhibited by cyclosporine A during acute cardiac allograft rejection in mice

作　　者：万云乐[1] 吴丽花[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 [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,浙江杭州310003

出　　处：《中国病理生理杂志》2005年第11期2123-2128,共6页Chinese Journal of Pathophysiology

基　　金：国家重点基础研究发展规划项目(国家973项目;No.2003CB515500)

摘　　要：目的研究小鼠同种心脏移植急性排斥反应中淋巴细胞趋化因子(lptn)的表达情况及环孢菌素A(cyclosporine A,CsA)的抑制作用。方法改良Banff评分系统判断同种小鼠移植心急性排斥反应程度,RT-PCR检测移植心组织内淋巴细胞趋化因子表达水平,ELISA方法检测心脏移植小鼠脾细胞活化T细胞核因子(NFAT)活性。结果C57BL/6-Balb/c急性排斥组小鼠移植术3d后脾脏显著增大。术后第5、7d移植心肌间淋巴细胞浸润程度评分分别为2.667±0.577和2.333±0.577。C57BL/6-Balb/c+CsA组小鼠移植术后脾脏肿大明显减轻,术后第5、7d心肌间淋巴细胞浸润程度评分分别为1.000±0.000和1.333±0.577。急性排斥组和CsA处理组小鼠移植心脏在术后第5d和第7d都可检测到Lptn mRNA阳性表达,但CsA处理组Lptn mRNA的表达明显弱于急性排斥组。治疗剂量的CsA可以完全抑制NFATc1活性。结论Lptn在早期移植免疫事件中具有重要的作用,CsA仅能部分抑制Lptn mR-NA的表达。活化T细胞Lptn的表达调控存在NFAT以外的途径。AIM： To investigate lymphotactin （Lptn） gene transcription during acute cardiac allograft rejection and the inhibitory effect of eyclosporine A （CsA）. METHODS： Graft specimens were harvested at indicated time to determine morphological changes by pathological examination. The grade of acute cardiac allograft rejection was evaluated by using modified Banff scoring system. Reverse transcription - polymerase chain reaction （ RT - PCR） was used to determine the Lptn mRNA expression in cardiac grafts. NFATcl activity of splenocytes after transplantation was assessed by enzyme- linked immunoabsordent assay （ELISA）. RESULTS： Prominent splenomegaly on day 3 posttransplantation was found in C57BL/6- Balb/c group. The extent of myocardial in- flammatory infiltration was scored 2.667 ± 0.577 at day 5 and 2.333 ± 0.577 at clay 7, respectively. Splenomegaly was ameliorated by CsA treatment, and the extent of myocardial infiltrate was scored 1.000 ± 0.000 at day 5 and 1.333 ± 0.577 at day 7, respectively. Lymphotactin mRNA was undetectable in cardiac isografts. Lymphotactin mRNA, which was inhibited partially by CsA, was upregulated strongly in acutely rejecting cardiac allografts at day 5 and day 7. Further studies demonstrated that NFATcl activity in splenocytes, which markedly upregulated during acute rejection, was completely inhibited by CsA. CONCLUSION： Lptn appears to be a key chemokine of lymphocyte infiltration during acute allograft rejection. Inhibition of NFATcl activity by CsA seems to decrease Lptn expression incompletely, suggesting that there was else mechanism to regulate Lptn expression other than NFAT pathway.

关 键 词：移植物排斥 心脏移植 淋巴细胞趋化因子 环孢菌素 小鼠 

分 类 号：R363[医药卫生—病理学]