Exogenous Hydrogen Sulfide Attenuates Cardiac Fibrosis Through Reactive Oxygen Species Signal Pathways in Experimental Diabetes Mellitus Models
Exogenous Hydrogen Sulfide Attenuates Cardiac Fibrosis Through Reactive Oxygen Species Signal Pathways in Experimental Diabetes Mellitus Models
复制标题
外源性硫化氢通过实验性糖尿病模型中的活性氧信号通路减轻心脏纤维化
DOI：
10.1159/000430266
复制
发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Zhong X, Zha
中科院分区：
文献类型：
--
作者：
Zheng D, Dong SY, Li T, Yang F, Yu XJ, Wu JC;Zhong X, Zha
工作背景：氧化应激诱导的高血糖和高糖在糖尿病心肌病相关的心脏纤维化的发展中起重要作用。内源性气体递质硫化氢（H2S）可以以细胞保护方式起作用。然而，H2S是否可以抑制纤维化过程尚不清楚。本研究的目的是探讨H2S在糖尿病性心肌病的发生和潜在机制中的作用。方法：采用链脲佐菌素（STZ）诱导大鼠糖尿病心肌病模型。高血糖和高糖诱导新生大鼠心脏成纤维细胞增殖和心肌纤维化。我们检测了GYY 4137（一种缓释H2S供体）、NaHS（一种外源性H2S供体）和NADPH氧化酶4（NOX 4）siRNA对活性氧（ROS）产生、MMP-2，9、胱硫醚-γ-裂解酶（CSE）、NOX 4和细胞外信号调节激酶1/2（ERK 1/2）的影响，以揭示H2S在糖尿病心肌病心脏纤维化中的作用。结果：在体内，NaHS处理抑制高血糖诱导的糖尿病心脏I型和III型胶原、MMP-2和MMP-9的表达。大鼠新生心脏成纤维细胞迁移和细胞存活的抑制管理GYY 4137。NOX 4的表达增加，高血糖和高糖，但减少在心脏成纤维细胞处理的NaHS和GYY 4137。GYY 4137和NOX 4 siRNA可降低大鼠新生心脏成纤维细胞ROS生成、ERK 1/2磷酸化以及MMP-2和MMP-9表达。结论：目前的研究表明，在糖尿病心肌病中，NOX 4表达增强通过ROS-ERK 1/2-MAPK依赖性机制导致心脏纤维化。NOX 4可能是H2S调节糖尿病心肌病心肌纤维化氧化还原稳态的重要靶点。
Background: Oxidative stress inducing hyperglycemia and high glucose play an important role in the development of cardiac fibrosis associated with diabetic cardiomyopathy. The endogenous gasotransmitter hydrogen sulfide (H2S) can act in a cytoprotective manner. However, whether H2S could inhibit the fibrotic process is unclear. The purpose of our study was to examine the role of H2S in the development and underlying mechanisms behind diabetic cardiomyopathy. Methods: Diabetic cardiomyopathy was induced in rats by injection of streptozotocin (STZ). Cardiac fibrosis and proliferation of rat neonatal cardiac fibroblasts were induced by hyperglycemia and high glucose. We tested the effects of GYY4137 (a slow-releasing H2S donor), NaHS (an exogenous H2S donor) and NADPH oxidase 4 (NOX4) siRNA on reactive oxygen species (ROS) production, MMP-2,9, cystathionine-γ-lyase (CSE), NOX4, and extracellular signal-regulated kinase 1/2 (ERK1/2) to reveal the effects of H2S on the cardiac fibrosis of diabetic cardiomyopathy. Result: In vivo, NaHS treatment inhibited hyperglycemia-induced expression of type I and III collagen, MMP-2 and MMP-9 in diabetic hearts. Rat neonatal cardiac fibroblast migration and cell survival were inhibited by administration of GYY4137. NOX4 expression was increased by hyperglycemia and high glucose, but was reduced in cardiac fibroblasts treated by NaHS and GYY4137. ROS production, ERK1/2 phosphorylation and MMP-2 and 9 expression were decreased in rat neonatal cardiac fibroblasts treated with GYY4137 and NOX4 siRNA. Conclusion: The present study shows that enhanced NOX4 expression results in cardiac fibrosis through ROS-ERK1/2-MAPkinase-dependent mechanisms in diabetic cardiomyopathy. NOX4 could be an important target for H2S to regulate redox homeostasis in cardiac fibrosis of diabetic cardiomyopathy.
登录
查看更多内容
DOI：
10.1126/science.1162667
发表时间：
2008-10-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Yang G;Wu L;Jiang B;Yang W;Qi J;Cao K;Meng Q;Mustafa AK;Mu W;Zhang S;Snyder SH;Wang R
通讯作者：
Wang R
影响因子：
37.8
作者：
Calvert JW;Elston M;Nicholson CK;Gundewar S;Jha S;Elrod JW;Ramachandran A;Lefer DJ
通讯作者：
Lefer DJ
DOI：
10.1126/stke.3492006re8
发表时间：
2006-08
期刊：
Science's STKE
影响因子：
--
作者：
M. Ushio-Fukai
通讯作者：
M. Ushio-Fukai
一种新型可控硫化氢释放分子可保护人类皮肤角质形成细胞免受甲基乙二醛引起的损伤和功能障碍。
DOI：
10.1159/000366339
发表时间：
2014
期刊：
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子：
--
作者：
Yang CT;Zhao Y;Xian M;Li JH;Dong Q;Bai HB;Xu JD;Zhang MF
通讯作者：
Zhang MF
影响因子：
--
作者：
Avanzato, Daniele;Merlino, Annalisa;Mancardi, Daniele
通讯作者：
Mancardi, Daniele