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环孢素与他克莫司诱导的原位小肠移植慢性移植物排斥反应大鼠模型的长期比较

Long-term comparison of rat model of chronic allograft rejection of orthotopic small bowel transplantation induced by cyclosporine versus tacrolimus.

作者信息

Li Y, Zhu Y, Wang J, Wei W, Wu B, Li J

机构信息

Department of Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

出版信息

Transplant Proc. 2013 Jun;45(5):1811-5. doi: 10.1016/j.transproceed.2012.12.012.

DOI:10.1016/j.transproceed.2012.12.012
PMID:23769050
Abstract

OBJECTIVE

To establish 2 models of long-term chronic allograft rejection (CR) of orthotopic small bowel transplantation (OSBT) using cyclosporine (CsA) or tacrolimus (FK506).

METHODS

F344 and Lewis rats served as donors and recipients respectively for OSBT. In the study 1, the rat was administered CsA (5 mg/kg/d) intramuscularly from postoperative day (POD) 0 to 13. In study 2, intramuscular FK 506 (0.3, 0.5, or 1.0 mg/kg/d) was delivered on POD 0-13, 20 and 27. We observed body weight gain, survival rate, and histology.

RESULTS

In study 1, all allografts demonstrated one or more histological features of CR but no serious villous blunting. In addition, there was no significant difference in the features of chronic allograft rejection between POD 60 and POD 90. In study 2, the rats that received FK506 at doses of 0.3 or 0.5 mg/kg/day survived to POD 126 but all died before OD 156. Recipients that were administered FK506 at a dose of 1.0 mg/kg/d survived beyond POD 180 showing the same body weight gain as the isogeneic group. Histopathologic analysis revealed distinctive features of CR in the rat models of OSBT induced by CsA or FK506.

CONCLUSION

Using CsA or FK506, we developed a rat CR model of OSBT; recipients administered FK506 survived longer and showed more classic characteristics of CR compared with those treated with CsA.

摘要

目的

使用环孢素(CsA)或他克莫司(FK506)建立原位小肠移植(OSBT)长期慢性移植物排斥反应(CR)的两种模型。

方法

分别采用F344和Lewis大鼠作为OSBT的供体和受体。在研究1中,大鼠从术后第0天(POD)至第13天肌肉注射CsA(5mg/kg/d)。在研究2中,于POD 0 - 13、20和27肌肉注射FK506(0.3、0.5或1.0mg/kg/d)。观察体重增加、生存率和组织学情况。

结果

在研究1中,所有同种异体移植物均表现出一种或多种CR的组织学特征,但无严重的绒毛变钝。此外,POD 60和POD 90之间慢性移植物排斥反应的特征无显著差异。在研究2中,接受0.3或0.5mg/kg/天剂量FK506的大鼠存活至POD 126,但均在OD 156之前死亡。接受1.0mg/kg/d剂量FK506的受体存活超过POD 180,体重增加情况与同基因组相同。组织病理学分析显示,CsA或FK506诱导的OSBT大鼠模型具有CR的独特特征。

结论

使用CsA或FK506,我们建立了OSBT的大鼠CR模型;与接受CsA治疗的大鼠相比,接受FK506治疗的受体存活时间更长,且表现出更典型的CR特征。

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