他克莫司与新型免疫抑制剂FK778或FK779联合应用预防大鼠心脏移植排斥反应

Synergistic effects of tacrolimus with FK778 or FK779 in prevention of acute heart allograft rejection in the rat

目的 评价他克莫司 (FK5 0 6 )与FK778或FK779联合应用预防大鼠心脏移植排斥反应的效果。方法 大鼠异位心脏移植后单独应用FK5 0 6、FK778和FK779进行免疫抑制治疗 ,并设联合用药组。结果 单独用药组与不用药对照组相比 ,移植心脏存活时间明显延长 ,FK779组尤其显著 ;联合用药组移植心脏存活时间不但比对照组明显延长 ,而且明显长于各药同剂量单用组 ,FK5 0 6与FK779合用组尤其显著。结论 FK5 0 6、FK778和FK779均有很强的免疫抑制效应 ,FK5 0

Objective Tacrolimus (FK506) and Malononitrilamides (MNA) 279 and 715 (FK778 and FK779) were tested for their mono- and combination-therapeutic effects in prevention of acute heart allograft rejection in the rat.Methods The rats were randomly divided into control group, mono-therapy group and combination-therapy group. All immunosuppressants were administered daily by gavage throughout the study.Results Compared with control group, mono-therapy group as well as combination-therapy group could significantly prolong cardiac allograft survival, combined therapy of FK778 or FK779 and FK506 produced additive or synergistic interaction when compared with monotherapy of each drug. Those synergistic effects were less strong in combination therapy of FK778 with FK506 than FK779 and FK506 at similar doses.Conclusions Combined therapy of FK778 or FK779 with FK506 produced additive or synergistic effect in prevention of acute cardiac rejection. FK779 oral formula is more potent that FK778 to prolong heart allograft survival in the rat.