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血红素加氧酶1与疟疾相关急性肺损伤/急性呼吸窘迫综合征中肺保护的关联

Association of Heme Oxygenase 1 with Lung Protection in Malaria-Associated ALI/ARDS.

作者信息

Pereira Marcelo L M, Ortolan Luana S, Sercundes Michelle K, Debone Daniela, Murillo Oscar, Lima Flávia A, Marinho Claudio R F, Epiphanio Sabrina

机构信息

Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.

Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil.

出版信息

Mediators Inflamm. 2016;2016:4158698. doi: 10.1155/2016/4158698. Epub 2016 Nov 15.

DOI:10.1155/2016/4158698
PMID:27974865
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5126464/
Abstract

Malaria is a serious disease, caused by the parasite of the genus , which was responsible for 440,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications in severe malaria. The murine model DBA/2 reproduces the clinical signs of ALI/ARDS in humans, when infected with ANKA. High levels of HO-1 were reported in cases of severe malaria. Our data indicated that the HO-1 mRNA and protein expression are increased in mice that develop malaria-associated ALI/ARDS (MA-ALI/ARDS). Additionally, the hemin, a HO-1 inducing drug, prevented mice from developing MA-ALI/ARDS when administered prior to the development of MA-ALI/ARDS in this model. Also, hemin treatment showed an amelioration of respiratory parameters in mice, high VEGF levels in the sera, and a decrease in vascular permeability in the lung, which are signs of ALI/ARDS. Therefore, the induction of HO-1 before the development of MA-ALI/ARDS could be protective. However, the increased expression of HO-1 on the onset of MA-ALI/ARDS development may represent an effort to revert the phenotype of this syndrome by the host. We therefore confirm that HO-1 inducing drugs could be used for prevention of MA-ALI/ARDS in humans.

摘要

疟疾是一种严重疾病，由疟原虫属寄生虫引起，2015年造成44万人死亡。急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）是重症疟疾的主要临床并发症之一。小鼠DBA/2模型在感染ANKA时会再现人类ALI/ARDS的临床症状。据报道，重症疟疾患者体内HO-1水平较高。我们的数据表明，在发生疟疾相关ALI/ARDS（MA-ALI/ARDS）的小鼠中，HO-1 mRNA和蛋白表达增加。此外，HO-1诱导药物血红素在该模型中MA-ALI/ARDS发生前给药时，可防止小鼠发生MA-ALI/ARDS。而且，血红素治疗可改善小鼠的呼吸参数，提高血清中VEGF水平，并降低肺血管通透性，这些都是ALI/ARDS的体征。因此，在MA-ALI/ARDS发生前诱导HO-1可能具有保护作用。然而，MA-ALI/ARDS发生时HO-1表达增加可能代表宿主试图逆转该综合征的表型。因此，我们证实HO-1诱导药物可用于预防人类MA-ALI/ARDS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a5/5126464/be951068db97/MI2016-4158698.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a5/5126464/105059348e50/MI2016-4158698.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a5/5126464/be94e8d9b609/MI2016-4158698.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a5/5126464/0882ed312046/MI2016-4158698.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a5/5126464/be951068db97/MI2016-4158698.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a5/5126464/105059348e50/MI2016-4158698.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a5/5126464/be94e8d9b609/MI2016-4158698.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a5/5126464/0882ed312046/MI2016-4158698.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98a5/5126464/be951068db97/MI2016-4158698.004.jpg

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