Effect of undercarboxylated osteocalcin on experimentally induced diabetic cardiomyopathy in male rats and its possible mechanisms of action /
تأثير الأوستيوكالسين الغير مكتمل الكربوكسيل علي اعتلال عضلة القلب السكري المعملي في ذكور الفئران و الآليات المحتملة له
Sarah Mahmoud Gamal Abdelaziz ; Supervised Maha Mohamed Gamal Eldin , Heba Mohamed Shawky , Laila Ahmad Rashed
- Cairo : Sarah Mahmoud Gamal Abdelaziz , 2015
- 251 P. : charts , facsimiles ; 25cm
Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Physiology
Methods: 56 adult male albino rats were divided into 6 groups (n=8/group): control group (further divided to control A and B), diabetic group, diabetic warfarin prophylaxis group, DCM untreated group, DCM warfarin treated group and normal warfarin treated group, for these groups, isolated heart function was assessed by measuring LV developed pressure, xP/xT and - xP/xT using powerlab data acquisition system aided by Langendorff heart perfusion apparatus. Blood samples were collected for measuring Fasting blood glucose and serum insulin as well as glycosylated hemoglobin and HOMA IR was calculated, besides, lipid profile was investigated by measuring serum triglycerides, VLDL and HDL for evaluation of risk factors in addition to serum ucOC and adiponectin. Cardiac tissue samples were taken to investigate malonaldehyde (MDA) content, acyl co-A dehydrogenase gene expression, TNF Ü, Bax/BCL2 ratio, VEGF gene expression and SERCA gene expression. Besides, the gene expression of OC receptor (GPRC6A) was assessed in the cardiac tissue.Results: According to the results of the current study, ucOC elevation via antagonizing the carboxylase enzyme using warfarin was accompanied by increased serum adiponectin and upregulated myocardial OC receptor in addition to favorable metabolic effects enhancing insulin secretion, lowering blood glucose and improving insulin sensitivity and lipid profile. Increased ucOC showed a protective effect against the development of DCM when administered as prophylaxix, and although not fully reversed, the condition of the myocardium was significantly improved when ucOC was elevated even after the settlement of DCM as a treatment. These favorable effects of ucOC were proved by functional assessment of isolated heart, which showed improvement in LV developed pressure systolic xP/xT, and diastolic - xP/xT. Further investigating the underlying mechanisms emphasized that effect, showing decreased cardiac MDA content, acyl co-A dehydrogenase gene expression, TNF Ü and Bax/BCL2 ratio, together with increased VEGF gene expression and SERCA gene expression