الفهرس 
Introduction and Aim of the workOnly 14 pages are availabe for public view
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Abstract
Diabetic bladder dysfunction (DBD) is a common health problem in
patients with diabetes mellitus (DM). It has received considerable
attention in the last decades due to its higher incidence than other diabetic
complications. Moreover, it adversely affects the quality of life of
diabetic patients, predisposing to debilitating complications. Oxidative
stress (OS) has emerged as potential pathologic mechanism in most of
diabetic complications; however the precise contribution of OS in DBD is
not totally addressed.
Manganese superoxide dismutase (MnSOD) represents the first line
of defense against OS, therefore generation of a mouse model with
conditional deletion of smooth muscle (SM)-specific Sod2 gene, that
encodes MnSOD, will be a promising tool to investigate the role of OS in
DBD.
The present work aimed mainly to:
1. Create a mouse model with conditional deletion of SM-specific
Sod2 using inducible Cre-LoxP recombination technique.
2. characterize the OS status in bladder detrusor SM, bladder
functions and morphology of the generated SM-specific Sod2 KO
mice.
3. Clarify the adverse effects of diabetes induction on bladder
remodeling and functions.
4. Elucidate the role of OS in the pathogenesis of DBD by comparing
the structural, functional and molecular changes of urinary bladder
in STZ-induced diabetic SM-specific Sod2 KO mice, with diabetic
wild type control mice.
5. Identify the possible correlations between the studied biomarkers.To achieve such objectives, the following parameters
were investigated:
Biochemical parameters:
• In blood: glucose and HbA1c.
• In bladder detrusor tissue:
- Antioxidant enzymes: the protein expressions and enzymatic
activities of MnSOD and Cu/ZnSOD
- OS markers: MDA and protein expression of nitrotyrosine.
- Apoptosis-related proteins: Bax, Bcl-2 and activated caspase-3
as well as calculation of Bax/Bcl-2 ratio.
- Nerve function-related proteins: the protein expression of NGF.
Histological study: representative samples of bladders of mice in
each group were processed for:
- Immunohistochemistry of MnSOD.
- Masson’s Trichrome staining and morphometric analysis of
tissue composition of bladder wall components.
Assessment of bladder function:
- 24 hours fluid consumption and urine output.
- Conscious CMG.
Experimental design:
The current study was divided into two parts, as follow:
Part I:
The SM-specific Sod2 KO mice were generated using the
inducible Cre-LoxP recombination technique. The SM-specific Sod2 KO
mice were compared with age matched wild type and SM-specific Cre
mice as two control groups for 12 weeks after the final dose of OHT
injection (n=24/genotype).