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霉酚酸酯和 FK506 对慢性移植肾肾病大鼠同种异体肾移植纤维化的影响不同。

Mycophenolate mofetil and FK506 have different effects on kidney allograft fibrosis in rats that underwent chronic allograft nephropathy.

机构信息

Department of Research and Education, Guizhou Province People's Hospital, Guiyang, China.

出版信息

BMC Nephrol. 2012 Jul 2;13:53. doi: 10.1186/1471-2369-13-53.

DOI:10.1186/1471-2369-13-53
PMID:22747784
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3470947/
Abstract

BACKGROUND

Tacrolimus (FK506) is associated with renal fibrosis in long-term use. Mycophenolatemofetil (MMF) can also inhibit or attenuate the progression of renal fibrosis. This study aimed to determine the different effects of FK506 and MMF on fibrosis-associated genes in the kidney in rats that underwent chronic allograft nephropathy (CAN).

METHODS

Fisher (F344) kidneys were orthotopically transplanted into Lewis rat recipients. All recipients were given Cyclosporin A (CsA) 10 mg/kg-1.d-1 × 10 day and were then randomly divided into three oral treatment groups (n = 9 in each group): (1) the vehicle group was given vehicle orally; (2) the FK506 group was given 0.15 mg/kg-1.d-1 FK506; and (3) the MMF group was given 20 mg/kg-1.d-1 MMF. At 4, 8, and 12 weeks post-transplantation, serum creatinine (SCr), collagen deposition, Connective tissue growth factor (CTGF), alpha smooth muscle actin (α-SMA) and E-cadherin expressions were determined and hematoxylin-eosin (HE) and Periodic acid-Schiff (PAS) stains were performed.

RESULTS

Renal function progressively deteriorated and showed typical CAN morphology in the vehicle and FK506 groups, while SCr and inflammatory infiltration (Banff score) showed a significant decrease in the MMF group after 8 weeks post-transplantation compared with those in the other groups (p < 0.05). Furthermore, expression levels of CTGF and α-SMA in the MMF group were significantly reduced, and the down-regulated expression of E-cadherin was abated (p < 0.05).

CONCLUSIONS

MMF showed favorable effects on renal interstitial fibrosis, thus efficiently retarding the progression of CAN.

摘要

背景

长期使用他克莫司（FK506）会导致肾纤维化。霉酚酸酯（MMF）也可以抑制或减轻肾纤维化的进展。本研究旨在确定 FK506 和 MMF 对接受慢性同种异体移植肾病（CAN）的大鼠肾脏纤维化相关基因的不同影响。

方法

将 Fisher（F344）肾脏原位移植到 Lewis 大鼠受体中。所有受体均接受环孢素 A（CsA）10mg/kg-1.d-1×10 天，然后随机分为三组口服治疗组（每组 9 只）：（1）载体组口服载体；（2）FK506 组给予 0.15mg/kg-1.d-1 FK506；（3）MMF 组给予 20mg/kg-1.d-1 MMF。移植后 4、8 和 12 周时，测定血清肌酐（SCr）、胶原沉积、结缔组织生长因子（CTGF）、α-平滑肌肌动蛋白（α-SMA）和 E-钙黏蛋白表达，并进行苏木精-伊红（HE）和过碘酸-希夫（PAS）染色。

结果

载体组和 FK506 组肾功能逐渐恶化，表现出典型的 CAN 形态，而 MMF 组在移植后 8 周时 SCr 和炎症浸润（Banff 评分）较其他组显著降低（p<0.05）。此外，MMF 组 CTGF 和α-SMA 的表达水平明显降低，E-钙黏蛋白的下调表达得到缓解（p<0.05）。

结论

MMF 对肾间质纤维化有良好的作用，从而有效延缓 CAN 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c5/3470947/391a03f2731f/1471-2369-13-53-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c5/3470947/42158c63901b/1471-2369-13-53-1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c5/3470947/bd1542fb95ed/1471-2369-13-53-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c5/3470947/391a03f2731f/1471-2369-13-53-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c5/3470947/42158c63901b/1471-2369-13-53-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c5/3470947/5f8baa5f612e/1471-2369-13-53-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c5/3470947/56d12d70a9b1/1471-2369-13-53-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90c5/3470947/5fec59cb5240/1471-2369-13-53-4.jpg
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