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环孢素A对幼鼠肾小球生长的影响以及咪唑立宾和氯沙坦对环孢素肾毒性的作用

Influence of cyclosporine A on glomerular growth and the effect of mizoribine and losartan on cyclosporine nephrotoxicity in young rats.

作者信息

Kim Ji Hong, Lee Yeon Hee, Lim Beom Jin, Jeong Hyeon Joo, Kim Pyung Kil, Shin Jae Il

机构信息

Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea.

出版信息

Sci Rep. 2016 Mar 7;6:22374. doi: 10.1038/srep22374.

DOI:10.1038/srep22374
PMID:26947764
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4780085/
Abstract

The aim of this study was to evaluate the influence of cyclosporine A (CsA) on glomerular growth and the effect of mizoribine (MZR) and losartan (LSAR) on CsA-induced nephropathy in young rats. Six-week-old male Sprague-Dawley rats maintained on a low salt diet were given CsA (15 mg/kg), CsA and LSRT (30 mg/kg/day), CsA and MZR (5 mg/kg), or a combination of CsA, LSRT, and MZR for 4 and 7 weeks (two experiments) and compared with control group (olive oil-treated). Histopathology and glomerular size, inflammatory and fibrotic factors were studied. The score of acute CsA toxicity significantly decreased in the CsA + MZR group compared to the CsA group (p < 0.01). MZR and MZR + LSRT reduced tubulointerstitial fibrosis and TGF-β1 mRNA expression at 7 weeks. Osteopontin (OPN) mRNA expression was decreased at 7 weeks in MZR + LSRT (p < 0.01). Glomerular area decreased CsA group and recovered in MZR (p < 0.01) and MZR + LSRT (p < 0.01) at 7 weeks. This study demonstrated that MZR and LSRT had suppressive effects on inflammatory process in chronic CsA nephropathy and led to improvement of tubular damage, tubulointerstitial fibrosis and arteriolopathy by down regulation of OPN and TGF-β1 and glomerular size contraction.

摘要

本研究旨在评估环孢素A（CsA）对幼鼠肾小球生长的影响，以及咪唑立宾（MZR）和氯沙坦（LSAR）对CsA诱导的肾病的作用。将维持低盐饮食的六周龄雄性Sprague-Dawley大鼠分为四组，分别给予CsA（15 mg/kg）、CsA与LSRT（30 mg/kg/天）、CsA与MZR（5 mg/kg），或CsA、LSRT和MZR的组合，持续4周和7周（两个实验），并与对照组（橄榄油处理）进行比较。研究了组织病理学、肾小球大小、炎症和纤维化因子。与CsA组相比，CsA + MZR组急性CsA毒性评分显著降低（p < 0.01）。MZR以及MZR + LSRT在7周时可减轻肾小管间质纤维化和TGF-β1 mRNA表达。MZR + LSRT组在7周时骨桥蛋白（OPN）mRNA表达降低（p < 0.01）。在7周时，CsA组肾小球面积减小，而MZR组（p < 0.01）和MZR + LSRT组（p < 0.01）肾小球面积恢复。本研究表明，MZR和LSRT对慢性CsA肾病的炎症过程具有抑制作用，并通过下调OPN和TGF-β1以及收缩肾小球大小，改善肾小管损伤、肾小管间质纤维化和小动脉病变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ad/4780085/0e021e19927d/srep22374-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ad/4780085/f840b4945ad1/srep22374-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ad/4780085/446a2542cf68/srep22374-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ad/4780085/2a3d4685425b/srep22374-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ad/4780085/0e021e19927d/srep22374-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ad/4780085/f840b4945ad1/srep22374-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ad/4780085/446a2542cf68/srep22374-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ad/4780085/2a3d4685425b/srep22374-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0ad/4780085/0e021e19927d/srep22374-f4.jpg

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本文引用的文献

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Pediatr Res. 2014 Jan;75(1-1):38-44. doi: 10.1038/pr.2013.169. Epub 2013 Oct 11.
2
Predictive factors for ciclosporin-associated nephrotoxicity in children with minimal change nephrotic syndrome.预测儿童微小病变性肾病综合征中环孢素相关肾毒性的因素。
J Clin Pathol. 2011 Jun;64(6):516-9. doi: 10.1136/jclinpath-2011-200005. Epub 2011 Mar 25.
3
Mizoribine: a new approach in the treatment of renal disease.
咪唑立宾：治疗肾脏疾病的新方法。
Clin Dev Immunol. 2009;2009:681482. doi: 10.1155/2009/681482. Epub 2009 Dec 13.
4
Protective effects of Mizoribine on Cyclosporine A nephropathy in rats.吗替麦考酚酯对大鼠环孢素 A 肾病的保护作用。
Pediatr Res. 2009 Nov;66(5):524-7. doi: 10.1203/PDR.0b013e3181b9b48a.
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Risk factors for cyclosporin A nephrotoxicity in children with steroid-dependant nephrotic syndrome.激素依赖型肾病综合征患儿环孢素A肾毒性的危险因素
Clin J Am Soc Nephrol. 2009 Sep;4(9):1409-16. doi: 10.2215/CJN.01520209. Epub 2009 Jul 23.
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Established and newly proposed mechanisms of chronic cyclosporine nephropathy.慢性环孢素肾病已确立的和新提出的机制。
Korean J Intern Med. 2009 Jun;24(2):81-92. doi: 10.3904/kjim.2009.24.2.81. Epub 2009 Jun 8.
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