机构:[1]Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China[2]Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China
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 hyperglycaemiainduced 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.
基金:
This work was supported by the National Natural Science Foundation
of China [grant numbers 81470501 and 81400292].
第一作者机构:[1]Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China[2]Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China
通讯作者:
通讯机构:[1]Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
推荐引用方式(GB/T 7714):
Xiang Zhou,Guoyin An,Xiang Lu.Hydrogen sulfide attenuates the development of diabetic cardiomyopathy[J].CLINICAL SCIENCE.2015,128(5):325-35.doi:10.1042/CS20140460.
APA:
Xiang Zhou,Guoyin An&Xiang Lu.(2015).Hydrogen sulfide attenuates the development of diabetic cardiomyopathy.CLINICAL SCIENCE,128,(5)
MLA:
Xiang Zhou,et al."Hydrogen sulfide attenuates the development of diabetic cardiomyopathy".CLINICAL SCIENCE 128..5(2015):325-35