THE NECESSITY OF DIFFERENTIAL IMMUNOSUPPRESSION FOR PREVENTION OF IMMUNE REJECTION BY FK506 IN RAT ISLET ALLOGRAFTS TRANSPLANTED INTO THE LIVER OR BENEATH THE KIDNEY CAPSULE
THE NECESSITY OF DIFFERENTIAL IMMUNOSUPPRESSION FOR PREVENTION OF IMMUNE REJECTION BY FK506 IN RAT ISLET ALLOGRAFTS TRANSPLANTED INTO THE LIVER OR BENEATH THE KIDNEY CAPSULE
复制标题
差异性免疫抑制对于预防移植到肝脏或肾囊下的大鼠胰岛同种异体移植物中 FK506 免疫排斥的必要性
DOI：
10.1097/00007890-199110000-00004
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发表时间：
1991
期刊：
影响因子：
6.2
通讯作者：
S. Ryu
中科院分区：
文献类型：
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作者：
S. Ryu
本研究的目的是利用FK506预防大鼠胰岛异体移植的免疫排斥反应。将WKA/Qdj （RT1u）胰岛通过链脲佐菌素（60 mg/kg）诱导的糖尿病Lewis （RT11）大鼠的门静脉（p.v.）或肾囊（k.c.）下移植到肝脏。新鲜或培养（24°C， 1周）胰岛作为供体。移植时植入含有5mg FK的微渗透泵（0.2 ml, Alzet 2001），在移植后7天内持续输送FK506。新鲜移植物的平均存活时间（MST）为61.4±37.2天（mean±SD, n=17）（对照组5.5±0.6,n=4）。17例患者中有10例在移植后90天以上血糖正常。采用低温培养胰岛，给予FK506 7 d，移植后90 d以上大鼠血糖均正常。新鲜和培养kc移植物的MST分别为22.0±14.2天和24.7±5.0天。长期反复植入含有5mg FK506的泵（5次，第0、7、14、21和28天），可显著延长新鲜或培养kc移植物的存活时间，MST分别为>58.7±22.1天和>56.9±18.0天。这些结果清楚地表明，通过移植后短期给药FK506和供体胰岛低温培养，可以预防肝脏移植的同种异体胰岛移植物的免疫排斥反应，同时也表明，长期持续给药FK506可以延长移植物的存活时间
The purpose of the present study was to achieve prevention of immune rejection in rat islet allografts by FK506. WKA/Qdj (RT1u) islets were transplanted either into the liver via the portal vein (p.v.) or beneath the kidney capsule (k.c.) of streptozotocin (60 mg/kg) induced diabetic Lewis (RT11) rats. Fresh or cultured (24°C, 1 week) islets were used as donors. A mini-osmotic pump (0.2 ml, Alzet 2001) containing 5 mg FK was implanted s.c. at the time of transplantation for continuous delivery of FK506 for 7 days after transplantation. The mean survival time (MST) of the fresh p.v. grafts with a pump was >61.4±37.2 days (mean ± SD, n=17) (control 5.5±0.6, n=4). Ten out of 17 were normoglycemic for more than 90 days after transplantation. When low-temperature cultured islets were used and FK506 was delivered for 7 days, all the rats were normoglycemic for more than 90 days after transplantation. The MST of the fresh or cultured k.c. grafts with a pump was 22.0±14.2 or 24.7±5.0 days, respectively. Long-term administration of FK506 by repeated implantations (5 times; days 0, 7, 14, 21, and 28) of pumps containing 5 mg FK506 produced marked prolongation of the fresh or cultured k.c. graft survival with an MST of >58.7±22.1 or >56.9±18.0 days, respectively. These findings clearly demonstrate that the prevention of immune rejection in the islet allografts transplanted into the liver was achieved by short-term post-transplant administration of FK506 and low-temperature culture of donor islets, and also show that long-term continuous administration of FK506 was needed for the prolongation of the graft survival when the renal