他克莫司联合青藤碱抑制大鼠心脏移植急性排斥反应  

Inhibition of acute rejection by tacrolimus and alkaloid sinomenine in rat heart transplantation

作　　者：徐广全[1] 金相元[1] 张策[1] 夏求明[1] 

机构地区：[1]哈尔滨医科大学附属第二医院胸外科,150086

出　　处：《中华器官移植杂志》2007年第4期229-231,共3页Chinese Journal of Organ Transplantation

摘　　要：目的 探讨青藤碱（SIN）对大鼠心脏移植急性排斥反应抑制作用的机制，并评价青藤碱与他克莫司（FK506）联合作用的效果。方法 以PVG大鼠为供者，DA大鼠为受者，建立同种异体心脏移植模型。将受者随机分为4组，每组20只。对照组：采用生理盐水3ml·kg^-1·d^-1灌胃；SIN组：腹腔注射SIN 30mg·kg^-1·d^-1；FK506组：采用FK506 0．25mg·kg^-1·d^-1灌胃；联合组：腹腔注射SIN 30mg·kg^-1·d^-1并联合应用FK506 0．25mg·kg^-1·d^-1灌胃。各组均在术后24h内用药，用药时间共7d。观察各组移植心存活时间，术后第7d取部分受者的移植心做病理检查，检测外周血中肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、T细胞亚群、一氧化氮合酶（iNOS）等的浓度。结果 对照组移植心平均存活时间为（6．0±1．054）d，FK506组为（10．2±2．2）d，SIN组为（9．5±1．84）d，联合组为（16．2±2．1）d，联合组与其他3组比较，差异有统计学意义（P〈0．05）。SIN组、FK506组及联合组与对照组比较，外周血中TNF-α、IFN-γ、iNOS的表达明显减少（P〈0．05），CD4^＋T细胞亚群增殖率也明显下降（P〈0．05）。其中联合组的效果更优于SIN组和FK506组（P〈0．05）。结论 SIN能明显地抑制大鼠心脏移植急性排斥反应的发生，与FK506联合应用有协同作用。Objective To discuss the inhibitory effects of alkaloid sinomenine （SIN） on acute rejection in rat heart transplantation and evaluate the effectiveness of sinomenine in combination with tacrolimus （FK506）. Methods All the recipients were divided into 4 groups at random： NS group, SIN group, FK506 group, and SIN ＋ FK506 group. Allografts of 10 recipients from each group were harvested at day 7 before end stage rejection for histological studies. The levels of TNF-α, IFN-γ, CD4^＋ , CD8^＋ T cell subsets and iNOS in peripheral blood were measured. Results The recipients in the NS group rejected their allografs at 7th day post-operation. Treatment with either SIN or FK506 could result in minimal prolongation of grafts survival, while treatment with SIN and FK506 led to a significant prolongation of graft survival. The expression of TNF-α, IFN-γ and iNOS was decreased in either SIN or FK506 group, and significantly in SIN ＋ FK506 group. The levels of CD4^＋ T cell subsets in peripheral blood of the SIN ＋ FK506 group were much lower than those of SIN group and FK506 group 7 days after transplantation. Conclusions SIN might play an immunosuppressive role in rat heart allograft models through inhibiting CD4^＋ T cell proliferation and down-regulating the levels of INF-γ, TNF-α and iNOS. SIN shows a significantly synergistic effect with FK506.

关 键 词：免疫抑制剂 心脏移植 移植物排斥 大鼠 

分 类 号：R686[医药卫生—骨科学]