الفهرس 
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Abstract
The present investigation was assigned to study and compare the effects of SGL2 inhibitor (dapagliflozin) to the insulin sensitizer (metformin) on experimentally - induced type II DM, regarding; glycemic state, lipid profile, ABP, cardiac performance, endothelial changes of thoracic aorta, and nucleic acid changes in cardiac &aortic tissues.
To achieve this goal, eighty adult male albino rats were used. They were divided into equally four experimental groups: non-diabetic, diabetic non-treated, diabetic metformin–treated and diabetic dapagliflozin-treated groups.
At the end of experimental period (4 weeks), ten rats from each group were anesthetized by using thiopental sodium (50 mg/kg (I.P), and midline laparotomy was done for invasive measuring of blood pressure (systolic &diastolic) by using 4-channel physiograph. MABP was then calculated. Three milliliters of fasting blood samples were collected directly from aortic cannula one milliliter was collected in EDTA containing tube for estimation of HbA1c,the other two milliliters were collected in plain tube for estimation of serum glucose, insulin, lipid profile (total cholesterol, triglycerides, LDL & HDL), MDA, TAC, and serum TNFα. Then HOMA -IR was calculated. After that the heart and aorta of each rat were excised and preserved at -80ᵒ for DNA extraction and determination of rate of flow of extracted myocardial DNA.
The other 10 rats from each group were cervically dislocated, then the chest wall of each rat was opened and the heart was excised and hooked from its apex. Cardiac contractility and heart rate were recorded using langendorff apparatus. Then thoracic aorta was fixed in 4% paraformaldehyde and processed through paraffin embedding and prepared for histopathological and immunohistochemical studies.
In the present investigation, Diabetes Mellitus type II rat model was successfully established in fat-fed rats injected with low dose streptozotocin (STZ-HFD) as evidenced by; a significant increase in glycemic index parameters FBG, HbA1c, serum insulin, and HOMA-IR. This was associated with significant elevation of TC, TG, LDL, MDA, TNF- and BP (SBP, DBP &MABP) ; while HDL, TAC and cardiac performance (contractility & rate) were significantly reduced when compared to the corresponding values of non –diabetic group.
Hypertension and cardiac impairment were proven in this STZ-HFD rat model by significant atherosclerotic histopathological changes by H&E, Masson trichome staining, and immunohistochemical staining with significant elevation of structural DNA damage in cardiac and aortic tissues compared to the non diabetic group.
Metformin treatment of diabetic rats with (100 mg/kg/day) for 4 weeks, revealed a statistically significant reduction of fasting serum glucose, HbA1c, serum insulin, HOMA-IR, TC, TG, LDL, MDA, TNF-α and BP (SBP, DBP &MABP); while HDL, TAC and cardiac performance (contractility & rate) were significantly higher when compared to the corresponding values of diabetic –non treated group.
These results were proven by histo-pathological and immune-histochemical studies. Sections of the thoracic aorta of the diabetic metformin-treated group illustrate slightly reduced changes of intimal endothelium. The thickness of the aortic wall was significantly reduced when compared to the diabetic-non treated group but the adventitia was still infiltrated by 40% by H&E staining. This was accompanied by a significant reduction of collagen fiber infiltration of aortic media seen with Masson trichrome stain with decrease in iNOS immunostaining intensity. Moreover, the mean value of DNA optical density was significantly reduced when compared to the corresponding value of the diabetic -non treated group.