Long-term moderate intensity exercise alleviates myocardial fibrosis in type 2 diabetic rats via inhibitions of oxidative stress and TGF-β1/Smad pathway

Exercise has an effect on the reduction of myocardial fibrosis in diabetic rats as previously reported, in which oxidative stress and the TGF-beta 1/Smad signaling pathway may play key roles. There is little direct experimental evidence that exercise alleviates myocardial fibrosis in type 2 diabetes mellitus (T2DM). Here we established a type 2 diabetic model by using streptozotocin and a high-fat diet. Rats were divided into groups of normal control (NC), T2DM and T2DM plus exercise (T2DME). The T2DME group received further treadmill training at moderate intensity for 8 weeks. Histological and biochemical methods were used to detect the benefits of exercise to T2DM. Results showed that the weight of rats in the T2DM group dropped dramatically, along with significant increases in blood glucose, myocardial fibrosis and oxidative stress, associated with upregulated expression of factors of myocardial fibrosis, except Smad7. Exercise largely reversed T2DM-induced alterations in factors of myocardial fibrosis, including suppressing expression of MMP-2, CTGF, TGF-beta 1, p-Smad2 and p-Smad3, and increased expression of TIMP-1 and Smad7. Therefore, exercise might be considered an alternative therapeutic remedy for diabetic cardiomyopathy.