Tabriz University of Medical Sciences Pharmaceutical Sciences 1735-403X 26 4 2020 12 25 The Combination Effect of Voluntary Exercise and Crocin on Angiogenic miRNAs in High-Fat Diet/Low-Dose STZ-Induced Type2 Diabetes in Rats: miR-126 and miR-210 379 385 10.34172/PS.2020.47 EN Hassan Dariushnejad https://orcid.org/0000-0003-2477-9461 Leila Chodari Vajihe Ghorbanzadeh https://orcid.org/0000-0002-4195-3516 Journal Article 10.34172/PS.2020.47 2019 11 30 2020 05 30 Background: As one of the major complications of diabetes, cardiovascular disease might result in early death in people with diabetes. miR-126 and 210 expressions undergo alterations in cardiac disease and cause heart failure. Methods: Animals were divided into the 5 groups of control (Con), diabetes (Dia), diabeticcrocin (Dia-Cro), diabetic-voluntary exercise (Dia-Exe), and diabetic-crocin-voluntary exercise (Dia-Cro-Exe). Type 2 diabetes was induced by the use of a high-fat diet (4 weeks) and injection of streptozotocin (STZ) (i.p, 35 mg/kg). Animals received crocin orally (50 mg/kg), and voluntary exercise was performed alone or together for 8 weeks. QRT–PCR method was used to determine the levels of miR-210 and miR-126 in cardiac tissue. Results: The levels of miR-210 and miR-126 in the cardiac tissue augmented in both the crocin and voluntary exercise groups in comparison with the non-treated group (p<0.001). The use of combination therapy with exercise and crocin magnified their effects on miR-210 and miR-126 levels (p<0.001). Moreover, MiR-210 levels were lower in the crocin group compared to the exercise group (p<0.001). Conclusion: The results indicated that voluntary exercise combined with crocin might provide a novel therapeutic plan for cardiovascular disease through increasing miR-210 and miR-126 expression.