糖尿病性心肌病
氧化应激
炎症
纤维化
医学
天狼星红
内科学
内分泌学
心脏纤维化
富马酸二甲酯
心功能曲线
心肌纤维化
糖尿病
促炎细胞因子
心肌病
链脲佐菌素
2型糖尿病
药理学
心力衰竭
免疫学
多发性硬化
作者
Xinyue Hu,Mohanraj Rajesh,Jian Zhang,Shanshan Zhou,Shudong Wang,Jian Sun,Yi Tan,Yang Zheng,Lu Cai
标识
DOI:10.1016/j.toxlet.2018.01.020
摘要
Oxidative stress and inflammation play key roles in the development of diabetic cardiomyopathy (DCM). Dimethyl fumarate (DMF), an FDA approved medicine for relapsing multiple sclerosis, has manifested its antioxidant and anti-inflammatory function mostly in the central nervous system. In this study, we investigated whether DMF could attenuate the development of DCM. Type 1 diabetes mouse model was established using multiple low-dose streptozotocin, and the diabetic mice were treated with DMF (10 mg/kg body weight) for 3 months. Cardiac functions were determined using echocardiography. Oxidative stress, pro-inflammatory cytokines and pro-fibrotic markers were determined with commercially available kits, real-time quantitative PCR or western blot techniques. DCM was characterized by diminished cardiac function, accompanied by oxidative stress and enhanced expression of pro-inflammatory cytokines. Diabetic cardiac tissue exhibited marked fibrosis, revealed by extracellular matrix deposition as determined by Sirius red staining of the myocardial tissues. Furthermore, Nrf2 and its downstream effectors were repressed in diabetic myocardium. On the contrary, diabetic animals treated with DMF exhibited blunted oxidative stress, inflammation, fibrosis and this correlated with Nrf2 activation. Our findings suggest that DMF could potentially thwart diabetes-induced myocardial tissue injury, likely via activation of Nrf2 function, providing firm impetus for future repurposing of DMF in the management of DCM.
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