الفهرس | Only 14 pages are availabe for public view |
Abstract Background: type 2 diabetes mellitus (DM) is the most prevalent type of DM and it is mainly related to inadequate response to insulin (reduced insulin sensitivity) and insulin resistance in peripheral tissues. Cardiovascular complications related to diabetes are major contributors in the morbidity and mortality of diabetic population. Among diabetesrelated cardiovascular complications, is diabetic cardiomyopathy (DCM) that refers to myocardial left ventricular dysfunction in absence of obvious coronary artery disease and atherosclerosis. There is a clear link between renin-angiotensin system hyperactivity and diabetes-induced myocardial injury. Therefore, angiotensin II receptor blockers have a possible protective role in DCM. Sodium–glucose cotransporter type 2 (SGLT2) inhibitors had approval to be used as anti-diabetic medications in the last decade. Independent of their anti-hyperglycemic effects, SGLT2 inhibitors have been shown in several experimental studies to have positive cardiovascular benefits. The present study was conducted to compare the cardioprotective effects of valsartan, an angiotensin II receptor blocker, and dapagliflozin (Dapa), SGLT2 inhibitor, and the possible underlying mechanisms, as well as the combined effect of both drugs against DCM in type 2 diabetic rats. Methods: 50 male albino rats were divided randomly into 5 groups (10 rats /group): control, diabetic group, valsartan treated group, Dapa treated group, valsartan and Dapa treated group. By the end of the study (9 weeks), rats were weighed and echocardiography was done. Also, serum fasting glucose, serum fasting insulin, HOMA-IR, serum IL6, IL8, myocardial GSH & MDA content and cardiac relative gene expression of MMP2, MEF2 and Bax/Bcl2 ratio were measured. In addition, cardiac histopathology (using Hematoxylin & Eosin and Masson trichrome stains), immunohistochemical stain of coronary microvasculature (CD31 immunoexpression) and morphometric studies for percentages of collagen fibers area and area of CD31immunoexpression were assessed. Results: diabetic group exhibited significant decline in systolic function, significant myocardial damage and fibrosis, significant weight loss, significant elevation in blood glucose, insulin, HOMA-IR, serum IL6, IL8, myocardial MDA and Bax/Bcl2 ratio. Also, diabetic rats showed significant decline in myocardial GSH and % area of CD31immunoexpression. Treatment of diabetic rats with valsartan or Dapa or combined therapy caused significant improvement of all assessed parameters. Conclusion: treatment of type 2 diabetic rats with valsartan or Dapa exhibited cardioprotective effects against DCM. There was no advance of administration of one drug above the other. But, higher cardioprotective effect was obtained with combined administration of both drugs. |