Dergiler / Türk Üroloji Dergisi/Turkish Journal of Urology / 2008 / Cilt: 34 - Sayı: 4
Sildenafil sitratın kısmi üreter obstrüksiyonu sonrası gelişen böbrek tübüler apoptozis üzerine etkisi: Deneysel çalışma
- Sayfa
- 463–468
- DOI
- —
Özet
Bu çalışmamızda sildenafil sitratın kısmi üreter obstrüksiyonun (PUUO) açılmasını takiben gelişen böbrek tübüler apoptozis ile endotelyal (eNOS) ve indüklenebilen nitrik oksit sentetaz (iNOS) ekspresyonları üzerine olan etkisini araştırmayı amaçladık.Otuz iki adet Wistar Albino sıçan randomize bir şekilde 4 gruba ayrıldı. Bir, iki ve üçüncü gruplara sol PUUO modeli oluşturuldu. Dördüncü grup ise sham grubu olarak kabul edildi. Bir ayın sonunda birinci grup obstrüksiyon düzeltilmeden sakrifiye edilirken üçüncü grup obstrüksiyonu düzeltilerek sakrifiye edildi. İkinci gruba ise obstrüksiyon açılmadan 4 saat önce oral yoldan sildenafil sitrat verildi. Tüm sıçanların sol böbrekleri histopatolojik incelemeler için çıkarıldı. Böbrek tübüler apopitotik hücre sayısı, sham grubunda 4,87±0,99 olarak bulunurken Grup 1’ de 12,75±0,88 olarak bulundu. Grup 3’de ortalama apopitotik hücre sayısı 15,75±0,46 idi ve bu değer tüm gruplar arasındaki en yüksek apopitozis oranını yansıtmaktaydı. Grup 2’deki sıçanlarda ise apopitotik hücre sayısının Grup 3’e oranla anlamlı derecede azaldığı gözlendi (p=0,002). Grup 1’deki eNOS ve iNOS ekspresyonları sham grubuna göre anlamlı derecede artmış olsa da bu değerler Grup 3’te Grup 1’e göre daha yüksekti (p=0,0001). Grup 2’de ise NOS ekspresyonları Grup 3’e göre anlamlı derecede azalmıştı (p=0,009 ve p=0,001). Kısmi üreter obstrüksiyonun açılmasından önce uygulanan tek doz sildenafil sitratın obstrüksiyonun açılmasının ardından böbrek dokusunda gözlenen artmış tübüler hücre apoptozisine karşı koruyucu etkisi gözlenmiştir.
Abstract
Introduction: Partial ureteral obstruction (PUUO) is one of the most common urologic problems in urological practice. It has been demonstrated that urinary tract obstruction induces progressive apoptosis of both renal tubular and interstitial cells. Tubular cell apoptosis is known as a major factor for the progressive renal tissue loss in obstructive uropathy. Sildenafil citrate is widely used for erectile dysfunction (ED). This drug is a phosphodiesterase 5 inhibitor and enhances cyclic guanosine monophosphate and nitric oxide mediated vasodilatation with resulting improvement of ED. The relationship between sildenafil citrate and apoptosis is already known. Sildenafil has been recently shown to have a strong protective effect against apoptosis through a NO signaling pathway. In this experimental study, we aimed to investigate the effect of sildenafil citrate on renal tubular apoptosis and endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) expressions after the release of partial unilateral ureteral obstruction. Materials and Method: Thirty-two Wistar Albino rats were randomly assigned into four groups. PUUO was formed in groups 1, 2 and 3. Group 4 was defined as sham group and received no drug. Experimental PUUO was created by placing an intravenous catheter into the ureter lumen and ligating the ureter and catheter together by using 4-0 silk suture. By ligating over the catheter, the ureters had been narrowed surgically. The catheter was then removed and the surgical incision was closed. Sham-operated rats had their ureters only manipulated. After one month, the rats in group 1 were sacrificed without repairing PUUO and the rats in group 3 were sacrificed after repairing PUUO. In group 2; sildenafil citrate (Viagra®, Pfizer, USA, 1 mg/day) was administered orally before 4 hours of repairing PUUO. Sildenafil citrate tablet was diluted with 10 cc distilled water to form a homogeneous solution and administered to rats orally. Left nephrectomy was performed for histopathological examination in all rats. Results: The mean number of renal tubular apoptotic cells was 4.87±0.99 in sham group and was 12.75±0.88 in group 1. The mean count was 15.75±0.46 in group 3 and this score reflected the highest apoptotic cell value in all groups. The mean apoptotic cell count was significantly decreased in group 2 according to group 3 (p=0.002). The expressions of eNOS and iNOS in group 1 were significantly increased according to sham group and these values were higher in group 3 than group 1 (p=0.0001). The NOS expressions were significantly decreased in group 2 according to group 3 (p=0.009 and p=0.001). Conclusion: Our findings demonstrate that PUUO increases renal tubular cell apoptosis and elevate NOSs concentrations in renal tubular tissue after partial ureteral obstruction. The oral administration of single dose of sildenafil citrate that is known to be effective in ED treatment before repairing of PUUO has a preventive effect against increased tubular cell apoptosis formed after repairing PUUO. In our opinion, these findings may be important in clinical situations. Our findings that will be supported with additional experimental studies may help physicians about using sildenafil citrate in the surgery day for PUUO.