Hydrogen sulfide attenuates the development of diabetic cardiomyopathy
Hydrogen sulfide attenuates the development of diabetic cardiomyopathy
复制标题
硫化氢可减轻糖尿病心肌病的发展。
DOI：
10.1042/cs20140460
复制
发表时间：
2015-03-01
期刊：
影响因子：
6
通讯作者：
Lu, Xiang
中科院分区：
文献类型：
--
作者：
Zhou, Xiang;An, Guoyin;Lu, Xiang
未标记
越来越多的证据表明H2S在治疗各种心血管疾病方面具有有益作用。然而，目前尚不清楚H2S是否可以减轻糖尿病心肌病（DCM）的发展。本研究旨在研究H2S对DCM的保护作用。通过腹腔注射链脲佐菌素诱导糖尿病大鼠，并给予H2S供体硫氢化钠（NaHS）16周。用核因子红细胞2相关因子2（Nrf 2）特异性siRNA转染或在高糖暴露前用SP 600125、SB 203580或LY 294002预处理的新生大鼠心肌细胞（NRCM）用于证实Nrf 2/抗氧化反应元件（ARE）的参与，丝裂原活化蛋白激酶（MAPK）和磷酸肌醇3-激酶（PI 3 K）/Akt信号通路在H2S的保护作用中的作用。超声心动图和组织病理学数据表明，H2S改善了糖尿病大鼠的左心室功能，防止了心肌肥厚和心肌纤维化。还发现H2S可减弱高血压诱导的炎症、氧化应激和心脏组织中的细胞凋亡。此外，H2S可激活Nrf 2/ARE信号通路，上调抗氧化蛋白血红素氧合酶-1（HO-1）和
NAD（P）H
醌氧化还原酶1（NQO 1）在糖尿病心肌。此外，发现H2S通过抑制c-Jun N-末端激酶（JNK）和p38 MAPK通路以及激活PI 3 K/Akt信号转导来减少高糖诱导的细胞凋亡。总之，我们的研究表明，H2S通过减轻炎症，氧化应激和细胞凋亡来抑制DCM的发展。
UNLABELLED
There is growing evidence that H2S has beneficial effects in treatment of various cardiovascular diseases. However, it remains unclear whether H2S can attenuate the development of diabetic cardiomyopathy (DCM). The present study was designed to investigate the protective effects of H2S against DCM. Diabetic rats were induced by intraperitoneal injection of streptozotocin and administered with the H2S donor sodium hydrosulfide (NaHS) for 16 weeks. Neonatal rat cardiomyocytes (NRCMs) transfected with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific siRNA or pre-treated with SP600125, SB203580 or LY294002 prior to high glucose exposure were used to confirm the involvement of Nrf2/antioxidant response element (ARE), mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/Akt signalling pathways in the protective effects of H2S. The echocardiographical and histopathological data indicated that H2S improved left ventricular function and prevented cardiac hypertrophy and myocardial fibrosis in diabetic rats. H2S was also found to attenuate hyperglycaemia-induced inflammation, oxidative stress and apoptosis in the cardiac tissue. In addition, H2S could activate the Nrf2/ARE signalling pathway and up-regulate the expression of antioxidant proteins haem oxygenase-1 (HO-1) and
NAD(P)H
quinone oxidoreductase 1 (NQO1) in the diabetic myocardium. Moreover, H2S was found to reduce high glucose-induced apoptosis both in vitro and in vivo by inhibiting c-Jun N-terminal kinase (JNK) and p38 MAPK pathways and activating PI3K/Akt signalling. In conclusion, our study demonstrates that H2S alleviates the development of DCM via attenuation of inflammation, oxidative stress and apoptosis.