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[环孢素和RS-61443治疗大鼠同种异体肢体显微外科移植排斥反应的控制]

[Control of the rejection process treated with cyclosporine and RS-61443, in allogeneic microsurgery transplantation of a limb, in rats].

作者信息

Ferreira L M, Anthony J P, Borsanyi J P, Benhaim P, Mathes S J, Laredo Filho J, Andrews J M

机构信息

Disciplina de Cirurgia Plástica da Escola Paulista de Medicina, São Paulo.

出版信息

Rev Assoc Med Bras (1992). 1995 Jan-Feb;41(1):11-9.

PMID:7550407
Abstract

Composite tissue allotransplantations would contribute to the reconstructions of the congenital, traumatic and tumors deformities. PURPOSE--The aim of this study is to prevent or inhibit the rejection in limb vascularized allotransplantation; decrease the toxicity of available immunosuppressive agents; determine whether combination subtherapeutic doses of CsA +RS-61443 will have an additive immunosuppressive effect. METHODS--Five groups were studied, using Brown-Norway limb donors and Fischer 344 recipient rats: group A Untreated autograft controls; group B Untreated allograft controls; group C Allografts: CsA 1.5 mg/kg/d SQ; group D Allograft: RS-61443 15 mg/kg/d; group E Allograft: combination CsA + RS-61443. RESULTS--The results were the following concerning the rejection: Group A animals displayed no rejection clinically (0%). All the skin biopsies obtained were devoid of rejection (grade 0). Group B animal developed rejection at 10-13 days post-transplantation. Skin biopsies confirmed the epidermal necrosis (grade 4). Group C animals developed rejection in 55%. Group D animals developed rejection in 94%. In contrast, Group E animals had 96% rejection-free survival up to POD 172 thus far. CONCLUSION--Combination subtherapeutic doses of CsA + RS-61443 was effective in preventing acute rejection of limb allografts and had an additive immunosuppressive effect because of the agents immunosuppressive synergistic effect.

摘要

复合组织同种异体移植将有助于先天性、创伤性和肿瘤性畸形的重建。目的——本研究的目的是预防或抑制肢体血管化同种异体移植中的排斥反应;降低现有免疫抑制剂的毒性;确定环孢素A(CsA)与RS - 61443的亚治疗剂量联合使用是否具有相加免疫抑制作用。方法——使用布朗 - 挪威肢体供体和费希尔344受体大鼠研究了五组:A组为未处理的自体移植对照组;B组为未处理的同种异体移植对照组;C组为同种异体移植:皮下注射CsA 1.5毫克/千克/天;D组为同种异体移植:RS - 61443 15毫克/千克/天;E组为同种异体移植:CsA与RS - 61443联合使用。结果——关于排斥反应的结果如下:A组动物临床上未出现排斥反应(0%)。所有获取的皮肤活检均无排斥反应(0级)。B组动物在移植后10 - 13天出现排斥反应。皮肤活检证实有表皮坏死(4级)。C组动物有55%出现排斥反应。D组动物有94%出现排斥反应。相比之下,E组动物截至术后第172天无排斥反应存活的比例为96%。结论——CsA与RS - 61443的亚治疗剂量联合使用可有效预防肢体同种异体移植的急性排斥反应,并且由于药物的免疫抑制协同作用而具有相加免疫抑制效果。

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