الفهرس 
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Abstract
Renal tubulo-interstitial fibrosis is a non-specific process, representing the final common pathway for all kidney diseases, one of the biggest problems in nephrology, indicates that patients inevitably reach ESRD. Urinary tract obstruction is a frequent cause of renal impairment. UUO is one of the most commonly applied rodent models to study the pathophysiology of renal fibrosis.
HMG-CoA reductase inhibitors, have anti-inflammatory, antiproliferative and immunomodulatory actions in vitro and in vivo. EPO has been demonstrated to play an important role as a novel cytoprotective agent in addition to the hematopoietic effects. Calcitriol offers a survival benefit in CRD patients and may help in preservation of renal functions. For progression of tubulointerstitial fibrosis aldosterone was reported to play a crucial role. Thus, it is considered that inhibition of mineralocorticoid receptor signaling with spironolactone to reduce interstitial fibrosis is a renoprotective action.
The present work aimed to study the effect of atorvastatin, erythropoietin vitamin D (calcitriol), and spironolactone on tubulointerstitial fibrosis and renal function in a rat model of PUUO.
Seventy rats were used and divided into 7 main groups, each consists of 10 rats as follow:
Group 1: Normal control group: Non operated rats, received saline IP and methyl cellulose orally for 14 days.
Group 2: Sham operated group, in which rats underwent the same surgical procedures as for PUUO(Group 3) including removal of the right kidney (right nephrectomy), but the left ureter was not obstructed and are received saline IP for 14 days.
Group 3: Rats underwent PUUO, received saline IP for 14 days after right nephrectomy and PUUO.
Group 4: Rats underwent PUUO and received atorvastatin in a dose of 50 mg/kg orally daily for 14 days from right nephrectomy and PUUO.
Group 5: Rats underwent PUUO and received erythropoietin in a dose of 3.000 IU/kg daily IP for 14 days from right nephrectomy and PUUO Group 6: Rats underwent PUUO and received calcitriol in a dose of 0.08 μg/kg daily IP for 14 days from right nephrectomy and PUUO.
Group 7: Rats underwent PUUO and received spironolactone in a dose of 50 mg/kg orally daily for 14 days from right nephrectomy and PUUO.
At the end of the experiment the following parameters were estimated :
1. Systolic blood pressure
2. Blood samples were collected to measure serum urea, creatinine, TGF-β and TNF-α.
3. Urine samples were collected for the determination of urinary protein and albumin concentration in addition to urinary creatinine to estimate creatinine clearance.
4. Determination of MDA level in the renal tissue homogenate.
5. Histopathological examination and immunohistochemical detection of α-SMA in the left kidney.
The results showed that there were marked deterioration of renal functions significant increase of SBP, serum cytokines, renal MDA level, urinary protein and albumin in addition to marked histopathological derangement all with increased α SMA expression after 14 days of PUUO indicating renal fibrosis in PUUOnontreated group compared to control group. Different treated groups showed significant improvement in all parameters except for SBP in EPO-treated, which showed nonsignificant change compared to PUUO-nontreated group.