الفهرس 
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Abstract
Abstract
Diabetic cardiomyopathy (DCM) is a major complication of diabetes
mellitus associated with structural and functional changes in the heart. Dapagliflozin
(DAPA) was shown to confer cardioprotection; however, its exact mechanisms are
not fully elucidated. Erythropoietin (EPO) simultaneously activates three pathways:
the Janus-activated kinase–signal transducer and activator of transcription
(JAK2/STAT5), phosphatidylinositol-3-kinase-Akt (PI3K/Akt), and extracellular
signal-related kinase (ERK/MAPK) cascades that result in proliferation and
differentiation of cardiac cells. In this study, DCM was induced by a high-fat diet
for 10 weeks, followed by administration of streptozotocin, (30mg/kg , I.P).
After confirmation of diabetes, rats were divided randomly into 5 groups:
group 1; normal control group, group 2; untreated diabetic group and Groups (3-5);
diabetic groups received DAPA daily (0.75 mg, 1.5 or 3 mg /Kg, p.o) respectively
for a month. At the end of the experiment, full anesthesia was induced in all rats
using ether inhalation, and ECG was recorded. Blood samples were collected, then
rats were sacrificed, and their hearts were dissected out and processed for
biochemical and histopathological studies. Untreated diabetic rats showed abnormal
ECG pattern, elevation of serum cardiac enzymes, decrease EPO levels,
downregulation of P-Akt, P-JAK2, and pMAPK pathways, abnormal histological
structure of the heart, and increase immunostaining intensity of P53 and TNF α in
the cardiomyocytes.
DAPA in a dose-dependent manner could improve ECG pattern, decrease the
myocardial and left ventricular weight indexes, mortality rate, and serum levels of
cardiac enzymes. It also could improve the histopathological structure of the heart
and reorganize of the cardiac myofibers. Moreover, DAPA could attenuate cardiac
fibrosis also could ameliorate immunohistochemical staining of TNF alpha and p53.
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Eventually, leading to, respectively, decrease inflammation and apoptosis in cardiac cells . The cardioprotective effect of DAPA could be mediated by increasing EPO levels and activation of P-Akt, P-JAK2, and pMAPK signaling cascades, which in turn decrease apoptosis.