Effect of mycophenolate mofetil, cyclosporin A, and both in combination in a murine corneal graft rejection model

Effect of mycophenolate mofetil, cyclosporin A, and both in combination in a murine corneal graft rejection model
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DOI:
10.1136/bjo.82.6.700
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发表时间:
1998-06-01
影响因子:
4.1
通讯作者:
Godehardt, E
Godehardt, E
中科院分区:
医学2区
文献类型:
--
作者:
Reis, A;Reinhard, T;Godehardt, E

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目的比较霉酚酸酯(MMF)、环孢素A(CSA)及两者联合应用预防角膜移植排斥反应的效果。方法以近交系Brown Norway和刘易斯大鼠分别作为供体和受体。在单药治疗和联合治疗中,以40 mg/kg体重的剂量经口给予MMF 14天,并以10 mg/kg体重的肌内剂量同样给予CSA 14天。每三天通过裂隙灯显微镜检查移植物。每一个移植进行组织学或免疫组织学evaluation.Results-The平均移植存活率在同种异体应变组合为7.9天(SEM 1.1)。单用霉酚酸酯可使移植存活期延长至11.6天,具有统计学意义(SEM 0.9,p< 0.05)。CSA单药治疗延迟移植排斥反应的时间在统计学上显著长于MMF(21天,0.0,p< 0.05)。CSA和MMF联合治疗在统计学上显著上级MMF单药治疗(22.3天,0.5,p< 0.05)。与CSA单一疗法相比,联合治疗延长了移植存活率,尽管没有达到统计学显著的程度。结论-在这项研究中,我们能够证明口服MMF对角膜移植后急性排斥反应的免疫抑制作用。CSA和MMF的双重药物治疗提供了边际效益,而没有更高的药物毒性或过度免疫抑制相关的并发症的发生率。
Aims-To compare the effectiveness of mycophenolate mofetil (MMF), cyclosporin A (CSA), and both in combination, in preventing rejection following corneal transplantations.Methods-Rats of the inbred strains Brown Norway and Lewis were used as donors and recipients respectively. MMF was administered orally in both monotherapy and combination therapy for 14 days in a dosage of 40 mg/kg body weight, and CSA was administered, likewise for 14 days, in an intramuscular dosage of 10 mg/kg body weight. The transplants were examined every third day by slit lamp microscopy. Every transplant was subjected to histological or immunohistological evaluation.Results-The average transplant survival rate in the allogenic strain combination was 7.9 days (SEM 1.1). Monotherapy with MMF led to a statistically significant prolongation of transplant survival to 11.6 days (SEM 0.9, p< 0.05). Monotherapy with CSA delayed transplant rejection statistically significantly longer than MMF (21 days, 0.0, p< 0.05). The combination therapy with CSA and MMF was statistically significantly superior to the monotherapy with MMF (22.3 days, 0.5, p< 0.05). The combination therapy prolonged transplant survival compared with the CSA monotherapy, albeit not to a statistically significant extent.Conclusions-In this study we were able to prove the immunosuppressive effect of oral MMF on acute rejection following corneal transplantation. Double drug therapy with CSA and MMF conferred a marginal benefit without a higher incidence of complications related to drug toxicity or overimmunosuppression.