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纳米复合材料治疗可降低急性移植物抗宿主病小鼠模型中的疾病发生率和致死率,并保留抗肿瘤效果。

Nanocomposite treatment reduces disease and lethality in a murine model of acute graft-versus-host disease and preserves anti-tumor effects.

作者信息

Bernardes Priscila T T, Rezende Bárbara M, Resende Carolina B, De Paula Talles P, Reis Alesandra C, Gonçalves William A, Vieira Elias G, Pinheiro Maurício V B, Souza Danielle G, Castor Marina G M, Teixeira Mauro M, Pinho Vanessa

机构信息

Laboratório de Resolução da Resposta Inflamatória, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Laboratório de Interação Microorganismo e Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

出版信息

PLoS One. 2015 Apr 13;10(4):e0123004. doi: 10.1371/journal.pone.0123004. eCollection 2015.

Abstract

Graft versus host disease (GVHD) is an immunological disorder triggered by bone marrow transplantation that affects several organs, including the gastrointestinal tract and liver. Fullerenes and their soluble forms, fullerols, are nanocomposites with a closed symmetrical structure with anti-inflammatory and anti-oxidant properties. The present study evaluated the effects of treatment with the fullerol (C60(OH)18-20) in the development and pathogenesis of GVHD in a murine model. Mice with experimental GVHD that were treated with the fullerol showed reduced clinical signs of disease and mortality compared with untreated mice. Treatment with the fullerol decreased the hepatic damage associated with reduced hepatic levels of reactive oxygen species, pro-inflammatory cytokines and chemokines (IFN-γ TNF-α, CCL2, CCL3 and CCL5) and reduced leukocyte accumulation. The amelioration of GVHD after treatment with the fullerol was also associated with reduced intestinal lesions and consequent bacterial translocation to the blood, liver and peritoneal cavity. Moreover, the fullerol treatment alleviated the GVHD while preserving effects of the graft against a leukemia cell line (GFP+P815). In summary, the fullerol was effective in reducing the GVHD inflammatory response in mice and may suggest novel ways to treat this disease.

摘要

移植物抗宿主病(GVHD)是一种由骨髓移植引发的免疫紊乱疾病,会影响包括胃肠道和肝脏在内的多个器官。富勒烯及其可溶形式富勒醇是具有封闭对称结构的纳米复合材料,具有抗炎和抗氧化特性。本研究评估了富勒醇(C60(OH)18 - 20)治疗对小鼠模型中GVHD发生发展及发病机制的影响。与未治疗的小鼠相比,接受富勒醇治疗的实验性GVHD小鼠的疾病临床症状和死亡率有所降低。富勒醇治疗降低了与肝脏活性氧水平、促炎细胞因子和趋化因子(IFN - γ、TNF - α、CCL2、CCL3和CCL5)水平降低相关的肝损伤,并减少了白细胞积聚。富勒醇治疗后GVHD的改善还与肠道病变减轻以及随之而来的细菌向血液、肝脏和腹腔的移位减少有关。此外,富勒醇治疗在减轻GVHD的同时保留了移植物对白血病细胞系(GFP + P815)的作用。总之,富勒醇在减轻小鼠GVHD炎症反应方面有效,可能为治疗这种疾病提供新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c869/4395348/30401cd0d2a1/pone.0123004.g001.jpg

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