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罗德里文 D1 给药在克氏锥虫感染中有益。

Resolvin D1 Administration Is Beneficial in Trypanosoma cruzi Infection.

机构信息

Division of Parasitology, Department of Pathology, Albert Einstein College of Medicine, New York, New York, USA.

Departamento de Ciências Biológicas, Programa de Pós-Graduação em Ciências Biológicas CBIOL/NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brazil.

出版信息

Infect Immun. 2020 May 20;88(6). doi: 10.1128/IAI.00052-20.

Abstract

Chagas disease is a major public health issue, affecting ∼10 million people worldwide. Transmitted by a protozoan named , this infection triggers a chronic inflammatory process that can lead to cardiomyopathy (Chagas disease). Resolvin D1 (RvD1) is a novel proresolution lipid mediator whose effects on inflammatory diseases dampens pathological inflammatory responses and can restore tissue homeostasis. Current therapies are not effective in altering the outcome of infection, and as RvD1 has been evaluated as a therapeutic agent in various inflammatory diseases, we examined if exogenous RvD1 could modulate the pathogenesis of Chagas disease in a murine model. CD-1 mice infected with the Brazil strain were treated with RvD1. Mice were administered 3 μg/kg of body weight RvD1 intraperitoneally on days 5, 10, and 15 to examine the effect of RvD1 on acute disease or administered the same dose on days 60, 65, and 70 to examine its effects on chronic infection. RvD1 therapy increased the survival rate and controlled parasite replication in mice with acute infection and reduced the levels of interferon gamma and transforming growth factor β (TGF-β) in mice with chronic infection. In addition, there was an increase in interleukin-10 levels with RvD1 therapy in both mice with acute infection and mice with chronic infection and a decrease in TGF-β levels and collagen content in cardiac tissue. Together, these data indicate that RvD1 therapy can dampen the inflammatory response, promote the resolution of infection, and prevent cardiac fibrosis.

摘要

恰加斯病是一个主要的公共卫生问题,影响着全球约 1000 万人。这种感染由一种名为 的原生动物传播,它引发慢性炎症过程,可导致心肌病(恰加斯病)。解析素 D1(RvD1)是一种新型的促解决脂介质,其对炎症性疾病的作用可以抑制病理性炎症反应,并恢复组织内稳态。目前的治疗方法不能有效改变 感染的结局,由于 RvD1 已在各种炎症性疾病中被评估为治疗剂,我们研究了外源性 RvD1 是否可以在小鼠模型中调节恰加斯病的发病机制。用 巴西株感染 CD-1 小鼠,并用 RvD1 处理。在第 5、10 和 15 天,通过腹腔内给予小鼠 3μg/kg 的体重 RvD1,以检查 RvD1 对急性疾病的影响;或者在第 60、65 和 70 天给予相同剂量的 RvD1,以检查其对慢性感染的影响。RvD1 治疗可提高急性感染小鼠的存活率和控制寄生虫复制,并降低慢性感染小鼠干扰素γ和转化生长因子-β(TGF-β)的水平。此外,RvD1 治疗可增加急性感染和慢性感染小鼠的白细胞介素-10 水平,并降低心脏组织中 TGF-β水平和胶原蛋白含量。总之,这些数据表明,RvD1 治疗可以抑制炎症反应,促进 感染的解决,并预防心脏纤维化。

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