Tacrolimus (FK506) and sirolimus (rapamycin) in combination are not antagonistic but produce extended graft survival in cardiac transplantation in the rat.
Tacrolimus (FK506) and sirolimus (rapamycin) in combination are not antagonistic but produce extended graft survival in cardiac transplantation in the rat.
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他克莫司 (FK506) 和西罗莫司（雷帕霉素）联合使用并不具有拮抗作用，但在大鼠心脏移植中可延长移植物的存活时间。
DOI：
10.1097/00007890-199712270-00039
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发表时间：
1997
期刊：
影响因子：
6.2
通讯作者：
H. Chen
中科院分区：
文献类型：
--
作者：
M. D. Vu;S. Qi;D. Xu;J. Wu;W. Fitzsimmons;S. Sehgal;L. Dumont;S. Busque;P. Daloze;H. Chen
联合使用他克莫司（FK 506）和西罗莫司（雷帕霉素[RAPA]）在大鼠血管化心脏移植模型中进行了检查。在预防急性排斥反应方面，从移植后第1天到第14天，低剂量FK 506和RAPA的三种不同组合均显著延长了心脏移植物的存活时间（P<0.05）。在持续急性排斥反应逆转模型中观察到相同的结果，其中从术后第4天至第18天低剂量FK 506和RAPA的两种组合也显示移植物存活时间显著长于单独使用每种免疫抑制剂（P<0.05）。在这两个模型中，所有低剂量治疗组的心脏移植物存活时间均显著长于未处理对照组（P<0.05），证实了这两种药物在所选模型中均为强效免疫抑制剂。这些结果还表明，与体外研究相比，FK 506和RAPA在体内联合使用并不产生拮抗作用，而是与单独使用每种药物相比，在延长同种异体移植物存活方面具有协同作用。似乎体内可用于结合的FKBP-12的丰度防止了两种药剂对其受体的抑制性竞争。
Combined use of tacrolimus (FK506) with sirolimus (rapamycin [RAPA]) was examined in a model of vascularized heart allograft in the rat. For prevention of acute rejection, three different combinations of low doses of FK506 and RAPA from day 1 up to day 14 after transplantation produced significantly longer cardiac allograft survival than each agent alone (P<0.05). Identical results were observed in a model of reversal of ongoing acute rejection, where two combinations of low doses of FK506 and RAPA from day 4 up to day 18 after surgery also demonstrated significantly longer graft survival than each immunosuppressant alone (P<0.05). All the low-dose-treated groups in these two models presented significantly longer heart graft survival than naive controls (P<0.05), confirming that both agents are potent immunosuppressants in the models chosen. These results also indicate that, in contrast with in vitro studies, the combined use of FK506 and RAPA in vivo did not produce antagonism, but rather had synergistic effect in prolonging the allograft survival as compared with each agent alone. It appears likely that the abundance of FKBP-12 available for binding in vivo prevents inhibitive competition of the two agents for their receptor.
口服西罗莫司和环孢素之间的药代动力学相互作用对协同延长大鼠同种异体心脏移植存活的影响。
影响因子：
6.2
作者：
Stepkowski,SM;Napoli,KL;Wang,ME;Qu,X;Chou,TC;Kahan,BD
通讯作者：
Kahan,BD