Mifepristone-inducible recombinant adenovirus attenuates paraquat-induced lung injury in rats

doi:10.1177/0960327114532381

科研成果详情

题名	Mifepristone-inducible recombinant adenovirus attenuates paraquat-induced lung injury in rats
作者	Hong G.-L.1; Cai Q.-Q.2; Tan J.-P.1; Jiang X.-Z.1; Zhao G.-J.1; Wu B.1; Li M.-F.1; Qiu Q.-M.1; Lu Z.-Q.1
发表日期	2015-01
发表期刊	HUMAN & EXPERIMENTAL TOXICOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	RU486 inducible regulation system NRF2 NF-B PQ poisoning
其他关键词	NF-KAPPA-B ; SUPEROXIDE-DISMUTASE ; EPITHELIAL-CELLS ; HEME OXYGENASE-1 ; NRF2 ; TOXICITY ; PATHWAY ; MECHANISMS ; EXPRESSION ; ACTIVATION
摘要	Objective: To investigate the effects of overexpression of nuclear factor E2-related factor-2 (NRF2) on lung injury in rats exposed to paraquat (PQ) poisoning. Methods: A mifepristone (RU486)-inducible recombinant adenoviral vector carrying the human NRF2 gene (Ad-RUNRF2) was constructed and transfected via airway into the rats 7 days before the administration of RU486. Rats were orally challenged with PQ at 20 mg/kg 24 h after the injection of RU486. On days 0.5, 3 and 21 after PQ poisoning, the expressions of NRF2 and cytokines related to inflammation and oxidation in lung tissue were examined. Results: RU486 remarkably enhanced NRF2 mRNA and NRF2 protein levels in Ad-RUNRF2-transfected rats in a dose-dependent manner (p < 0.01). PQ stimulated compensatory overexpression of NRF2, heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1) in lungs on days 0.5 and 3 after exposure (p < 0.05), but depleted the expression of catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH), with an increased malondialdehyde (MDA) (p < 0.05). However, pretreatment with Ad-RUNRF2 and RU486 strongly enhanced the expression levels of NRF2, HO-1, NQO-1, CAT and GSH-Px in the lungs of PQ intoxicated rats, with increased GSH and decreased MDA (p < 0.05). Pretreatment with Ad-RUNRF2 and RU486 also strongly suppressed the PQ-induced activation of nuclear factor B (NF-B) and decreased the levels of tumour necrosis factor- (TNF-), interleukin-1 (IL-1) and interleukin-6 (IL-6). In addition, Ad-RUNRF2 and RU486 induction significantly reduced PQ-induced pathological changes in lungs and attenuated lung oedema and protein leakage caused by PQ (p < 0.05). Conclusion: RU486-induced overexpression of NRF2 in lungs transfected with Ad-RUNRF2 can ameliorate PQ-induced lung injury by the activation of the NRF2-antioxidant response element (ARE) pathway.
资助项目	Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [Y2080977]; Core Project of Medicine and Health Care Platform in Zhejiang Province [2012RCA040]; Key Discipline Construction Project of Colleges and universities in Zhejiang Province; key construction academic subject (medical innovation) of Zhejiang Province [11-CX26]
出版者	SAGE PUBLICATIONS LTD
出版地	LONDON
ISSN	0960-3271
EISSN	1477-0903
卷号	34 期号:1 页码:32-43
DOI	10.1177/0960327114532381
页数	12
WOS类目	Toxicology
WOS研究方向	Toxicology
WOS记录号	WOS:000346643700004
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	24812154
SCOPUSEID	2-s2.0-84919665461
通讯作者地址	[Lu Z.-Q.]Department of Emergency Medicine, First Affiliated Hospital, Wenzhou Medical University,Shangcai Village, Nanbaixiang Town, Ouhai District,Wenzhou, Zhejiang,325000,China
Scopus学科分类	Toxicology;Health, Toxicology and Mutagenesis
引用统计	被引频次：9[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/15558
专题	第一临床医学院（信息与工程学院）、附属第一医院_急诊医学附属第一医院
通讯作者	Lu Z.-Q.
作者单位	1.Department of Emergency Medicine, First Affiliated Hospital, Wenzhou Medical University,Shangcai Village, Nanbaixiang Town, Ouhai District,Wenzhou, Zhejiang,325000,China; 2.Emergency Intensive Care Unit, First People's Hospital,Taizhou, Zhejiang,China
第一作者单位	附属第一医院
通讯作者单位	附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Hong G.-L.,Cai Q.-Q.,Tan J.-P.,et al. Mifepristone-inducible recombinant adenovirus attenuates paraquat-induced lung injury in rats[J]. HUMAN & EXPERIMENTAL TOXICOLOGY,2015,34(1):32-43.
APA	Hong G.-L.., Cai Q.-Q.., Tan J.-P.., Jiang X.-Z.., Zhao G.-J.., ... & Lu Z.-Q.. (2015). Mifepristone-inducible recombinant adenovirus attenuates paraquat-induced lung injury in rats. HUMAN & EXPERIMENTAL TOXICOLOGY, 34(1), 32-43.
MLA	Hong G.-L.,et al."Mifepristone-inducible recombinant adenovirus attenuates paraquat-induced lung injury in rats".HUMAN & EXPERIMENTAL TOXICOLOGY 34.1(2015):32-43.