葉力森2006-07-262018-07-092006-07-262018-07-091998http://ntur.lib.ntu.edu.tw//handle/246246/28666肢體異體移植因為其組成組織之複雜及高抗原性，在免疫學上一直具有極高 的難度。在我們較早的研究中，leflunomide (LEF)合用環孢靈(cyclosporine, CsA)已能 有效控制不相容肢體之異體移植，且恢復 理想之肢體功能。因為新一代的免疫抑制 劑FK506 有高於cyclosporine 的藥效，有 增加組織對抗缺氧的能力，而且常常能夠 引發其它動物模式之免疫耐性出現，本研 究中採用相同之動物組合， 研究 leflunomide(LEF)及FK-506 的組合對於異 體肢體移植之影響。Brown-Norway 大鼠 之帶血管/皮膚/肌肉/骨骼瓣用於移植至 Lewis 大鼠身上。實驗組中接受者於手術 前1 日開始投與LEF (10mg/kg/24hr/PO)， 以及FK-506 (0.1 or 0.5 mg/kg/24hr/SC)， 或CsA (Neoral, 5mg/kg/24hr/PO)。此免疫 抑制治療持續至移植後30 日或至肢體產 生排斥反應為止。所有實驗組大鼠在投藥 期間均存活，且沒有排斥及GVHD 症狀出 現。採用FK-506 0.1 mg/kg 劑量處理之大 鼠有75%於停藥後20 日出現排斥現象， 且經回復投藥無法逆轉。採用FK-506 0.5 mg/kg 處理之動物，則於停藥後100 日仍 未出現排斥作用。於術後30 日停藥後， 所有CsA 治療組動物多在二週內發生排 斥。每一個實驗組在停藥後均沒有發生 GVHD。本研究目前顯示，以LEF 及 FK-506 之組合，優於先前之LEF 與CsA 之組合，對於免疫抗原性特高之肢體組 織，仍能成功引發組織耐性，這是以往文 獻所不曾出現的現象，值得深入研究。Whole limb allotransplantation presents a tremendous immunologic challenge due to the antigenicity of skin, muscle and bone marrow. In our previous study, leflunomide (LEF) combined with cyclosporine (CsA) prevented limb allograft rejection across a strong histocompatibility barrier. Using the same model, LEF plus FK506, a new immunosuppressant with higher efficiency than CsA, was administered to rats receiving vascularized osteo-myo-cutaneous allografts. Vascularized osteo-myo-cutaneous of rear limbs were transplanted from Brown- Norway to Lewis rat recipients. Recipients were administered LEF (10 mg/kg/24hr/PO) and FK506 (0.1 or 0.5 mg/kg/24hr/SC) or CsA (Neoral, 5mg/kg/24hr/PO) starting 1 days prior to surgery. Treatment continued for 30 days or until graft rejection. All treated allografts survived the 30 day period without signs of rejection and GVHD. In the group treated with FK506 0.1mg/kg, 75% recipients showed rejection 20 days after cessation of treatment. No rejection presented in those recipients treated with FK506 0.5mg/kg over 100 days after cessation of treatment. All recipients treated by CsA showed rejection within 2 week after cessation of treatment. According to the result of this research, combination of LEF and FK506 can induce immune tolerance in the high antigenetic limb transplantation. We never review similar report in other article.application/pdf50175 bytesapplication/pdfzh-TW國立臺灣大學獸醫學系暨研究所肢體移植排斥移植物宿主病reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/28666/1/872313B002095.pdf