الفهرس 
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Abstract
In the present study, we investigated the role of PARP-1 enzyme in the development of cardiovascular complications in T2D rats. Type 2 diabetes mellitus (T2DM) was induced in rats by high-fructose/ high-fat diet beside streptozotocin injection, the model which was accompanied by cardiovascular complications.
The effect of PARP-1 enzyme inhibition by 4-aminobenzamide (4-AB) (and olaparib in some experiments) was investigated. To examine mechanisms by which PARP-1 mediates diabetic cardiovascular complications, cardiac conductivity and blood pressure were recorded. Also, vascular reactivity to the standard vasoconstrictor; phenylephrine (PE) was examined using both the isolated artery and the isolated perfused kidney techniques. In addition, serum levels of glucose, fructosamine, insulin, TNF-α, triglycerides, total cholesterol, HDL-cholesterol, creatinine and urea were determined. PARP-1 activity, nitric oxide products (nitrites and nitrates) as well as antioxidant parameters: reduced glutathione (GSH) and superoxide dismutase (SOD) were measured in tissue homogenate of the heart and kidney. Kidney functions; urinary albumin excretion, urinary total protein, blood urea nitrogen and creatinine clearance were determined to illustrate the role of PARP in DN. Moreover, examination of general histology as well as collagen deposition was carried out in heart, kidney and aorta sections to confirm and further illustrate results from the biochemical analysis.
The main findings can be summarized as following:
Part I: PARP-1 inhibition alleviates diabetic cardiovascular complications in experimental animals
1. PARP-1 activity was increased in the myocardium while significantly inhibited by 4-AB treatment.
2. The current model of DM was associated with cardiac conductivity disturbances; atrioventricular block and myocardial ischemia, which were completely prevented by PARP-1 inhibition.
3. DM was accompanied by elevation in the diastolic and mean arterial pressures which were decreased by PARP-1 inhibition.
4. Diabetes increased the contractile response of aorta and kidney to the vasoconstrictor; PE and PARP-1 inhibition reduced this exaggerated response.
5. Diabetes induced a state of low grade inflammation and PARP inhibition reduced it.
6. Diabetes was associated with oxidative stress in the heart and this was alleviated by PARP-1 inhibition7. Diabetes caused many pathological structural changes in the heart and aorta, mainly; inflammation, endothelial destruction and increased collagen deposition, the features which were improved by PARP-1 inhibition.