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NecroX-5通过调节缺氧/复氧处理的大鼠心脏中的TNFα/Dcn/TGFβ1/Smad2信号通路发挥抗炎和抗纤维化作用。

NecroX-5 exerts anti-inflammatory and anti-fibrotic effects via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway in hypoxia/reoxygenation-treated rat hearts.

作者信息

Thu Vu Thi, Kim Hyoung Kyu, Long Le Thanh, Thuy To Thanh, Huy Nguyen Quang, Kim Soon Ha, Kim Nari, Ko Kyung Soo, Rhee Byoung Doo, Han Jin

机构信息

National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.; VNU University of Science, Hanoi 120036, Vietnam.

National Research Laboratory for Mitochondrial Signaling, Department of Physiology, Department of Health Sciences and Technology, BK21 Project Team, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.; Department of Integrated Biomedical Science, College of Medicine, Inje University, Busan 47392, Korea.

出版信息

Korean J Physiol Pharmacol. 2016 May;20(3):305-14. doi: 10.4196/kjpp.2016.20.3.305. Epub 2016 Apr 26.

Abstract

Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating infl ammation and fi brosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 (10 µmol/L) treatment as experimental models. Addition of NecroX-5 signifi cantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 (TGFβ1) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, signifi cantly increased production of tumor necrosis factor alpha (TNFα), TGFβ1, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of TNFα, TGFβ1, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway.

摘要

在再灌注期,炎症和纤维化反应加速,过度的纤维化和炎症会导致心脏功能障碍。已证明NecroX化合物可保护肝脏和心脏免受缺血 - 再灌注损伤。本研究的目的是进一步确定NecroX - 5在缺氧/复氧(HR)模型中调节炎症和纤维化反应的作用及作用机制。我们将经HR处理的大鼠心脏和在有或无NecroX - 5(10 μmol/L)处理情况下经脂多糖(LPS)处理的H9C2培养细胞作为实验模型。添加NecroX - 5可显著增加经HR处理心脏中核心蛋白聚糖(Dcn)的表达水平。相反,在经NecroX - 5处理的心脏中,转化生长因子β1(TGFβ1)的表达和Smad2磷酸化(pSmad2)明显减弱。此外,在LPS刺激的H9C2细胞中观察到肿瘤坏死因子α(TNFα)、TGFβ1和pSmad2的产生显著增加,而Dcn表达水平明显降低。有趣的是,补充NecroX - 5可有效减弱TNFα、TGFβ1和pSmad2表达水平的升高以及Dcn表达的降低。因此,我们的数据表明NecroX - 5通过调节TNFα/Dcn/TGFβ1/Smad2途径对心脏HR损伤具有潜在的抗炎和抗纤维化作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6a/4860373/be0531103b45/kjpp-20-305-g001.jpg

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